bluuebunny/crossref_metadata_2025 huggingface dataset:
Accidental hypothermia in recreational activities in the mountains: A narrative review
Authors: Procter Emily , Brugger Hermann , Burtscher Martin
Published: September 2018

The popularity of recreational activities in the mountains worldwide has led to an increase in the total number of persons exposed to cold and extreme environments through recreation. There is little conclusive evidence about the risk of hypothermia for specific activities or populations, nor is it clear which activities are represented in the literature. This is a non‐systematic review of accidental hypothermia in different recreational activities in the mountains, with a specific focus on outdoor or winter activities that potentially involve cold exposure. Cases of hypothermia have been reported in the literature in mountaineering, trekking, hiking, skiing, activities performed in the backcountry, ultra‐endurance events, and databases from search and rescue services that include various types of recreation. Of these activities, hypothermia as a primary illness occurs most commonly during mountaineering in the highest elevation areas in the world and during recreation practiced in more northern or remote areas. Hypothermia in skiers, snowboarders, and glacier‐based activities is most often associated with accidents occurring off‐piste or in the backcountry (crevasse, avalanche). Organizers of outdoor events also have a role in reducing the incidence of hypothermia through medical screening and other preparedness measures. More complete collection and reporting of data on mild hypothermia and temperature measurement would improve our understanding of the incidence of hypothermia in outdoor recreation in future.
Response of protein S100B to playing American football, lifting weights, and treadmill running
Authors: Rogatzki Matthew J. , Keuler Sydney A. , Harris Abigail E. , Ringgenberg Scott W. , Breckenridge Ryanne E. , White Jeffrey L. , Baker Julien S.
Published: September 2018

Objective

To determine if serum S100B increases similarly as a result of playing American football compared to exercise alone.

Methods

Serum S100B was measured in division III collegiate football players before and after every home game during a single football season. Serum S100B was also measured before and after subjects walked on a treadmill for 30 minutes at a leisurely pace, ran on a treadmill while wearing and not wearing a football helmet at 6 mph for 8 minutes, and performed low‐, moderate‐, or high‐intensity resistance exercise.

Results

Serum S100B increased significantly (P < 0.05) when subjects played in a football game, ran on a treadmill, or performed moderate‐intensity resistance exercise. Pre‐game serum S100B did not accumulate throughout the football season in any of the players (P > 0.05). The increase in serum S100B during football games was moderately and significantly correlated with both the number of hits (R2 = 0.407) and the number of plays (R2 = 0.484) that each player experienced (P < 0.001). Post‐game serum S100B was greater in football players who played more than 50 plays compared to those players who played <50 plays, subjects who exercised on a treadmill, or subjects performing resistance exercise (P < 0.05).

Conclusion

It is unclear if the higher S100B concentration in football players playing at least 50 plays was caused by exercise or hits. Therefore, if serum S100B is to be used as a biomarker of impacts, and possible brain injury in sport, exercise time and intensity should be taken into account as confounding variables.
Addressing racial inequalities within schools: Exploring the potential of teacher education
Authors: Alvaré Melissa Archer
Published: September 2018

A substantial body of literature demonstrates how within‐school patterns serve to maintain and perpetuate racial inequality in education. This occurs as well‐meaning teachers and administrators tend to hold lower academic expectations for students of color; engage in racially biased discipline patterns; employ alienating curricula; and fail to address racial issues in meaningful ways when they surface in classrooms. In this paper, I review literature on these and other inequitable patterns and subsequently summarize research exploring how these issues are confronted teacher training programs. While some pedagogical models show promise, many studies suggest that multicultural education and programs for pre‐service teachers fall short in promoting perspectives and practices to address inequity in schools. I apply tenets of critical race theory to scrutinize oppression within schools and the shortcomings of initiatives claimed to redress them, and moreover, to suggest how teacher education can be improved to encourage pedagogy for social justice ends.
Reactivation of Chagas disease among heart transplant recipients in the United States, 2012‐2016
Authors: Gray Elizabeth B. , La Hoz Ricardo M. , Green Jaime S. , Vikram Holenarasipur R. , Benedict Theresa , Rivera Hilda , Montgomery Susan P.
Published: September 2018

Background

Heart transplantation has been shown to be a safe and effective intervention for progressive cardiomyopathy from chronic Chagas disease. However, in the presence of the immunosuppression required for heart transplantation, the likelihood of Chagas disease reactivation is significant. Reactivation may cause myocarditis resulting in allograft dysfunction and the rapid onset of congestive heart failure. Reactivation rates have been well documented in Latin America; however, there is a paucity of data regarding the risk in non‐endemic countries.

Methods

We present our experience with 31 patients with chronic Chagas disease who underwent orthotopic heart transplantation in the United States from 2012 to 2016. Patients were monitored following a standard schedule.

Results

Of the 31 patients, 19 (61%) developed evidence of reactivation. Among the 19 patients, a majority (95%) were identified by laboratory monitoring using polymerase chain reaction testing. One patient was identified after the onset of clinical symptoms of reactivation. All subjects with evidence of reactivation were alive at follow‐up (median: 60 weeks).

Conclusions

Transplant programs in the United States are encouraged to implement a monitoring program for heart transplant recipients with Chagas disease. Our experience using a preemptive approach of monitoring for Chagas disease reactivation was effective at identifying reactivation before symptoms developed.
Characterization and cost–benefit analysis of automated bioreactor‐expanded mesenchymal stem cells for clinical applications
Authors: Russell Athena L. , Lefavor Rebecca C. , Zubair Abba C.
Published: September 2018

BACKGROUND

Expanding quantities of mesenchymal stem cells (MSCs) sufficient to treat large numbers of patients in cellular therapy and regenerative medicine clinical trials is an ongoing challenge for cell manufacturing facilities.

STUDY DESIGN AND METHODS

We evaluated options for scaling up large quantities of bone marrow–derived MSCs (BM‐MSCs) using methods that can be performed in compliance with Good Manufacturing Practices (GMP). We expanded BM‐MSCs from fresh marrow aspirate in αMEM supplemented with 5% human platelet lysate using both an automated cell expansion system (Quantum, Terumo BCT) and a manual flask‐based method using multilayer flasks. We compared MSCs expanded using both methods and assessed their differentiation to adipogenic and osteogenic tissue, capacity to suppress T‐cell proliferation, cytokines, and growth factor secretion profile and cost‐effectiveness of manufacturing enough BM‐MSCs to administer a single dose of 100 × 106 cells per subject in a clinical trial of 100 subjects.

RESULTS

We have established that large quantities of clinical‐grade BM‐MSCs manufactured with an automated hollow‐fiber bioreactor were phenotypically (CD73, CD90, CD105) and functionally (adipogenic and osteogenic differentiation and cytokine and growth factor secretion) similar to manually expanded BM‐MSCs. In addition, MSC manufacturing costs significantly less and required less time and effort when using the Quantum automated cell expansion system over the manual multilayer flasks method.

CONCLUSION

MSCs manufactured by an automated bioreactor are physically and functionally equivalent to the MSCs manufactured by the manual flask method and have met the standards required for clinical application.
Patient blood management in colorectal cancer patients: a survey among Dutch gastroenterologists, surgeons, and anesthesiologists
Authors: Wilson Michael J. , Koopman‐van Gemert Ankie W.M.M. , Harlaar Joris J. , Jeekel Johannes , Zwaginga Jaap Jan , Schipperus Martin
Published: September 2018

INTRODUCTION

There is an increasing awareness to integrate patient blood management (PBM) within routine surgical care. Limited information about the implementation of PBM in colorectal cancer surgery is available. This is curious, as preoperative anemia, associated with increased morbidity, is highly prevalent in colorectal cancer patients. Present study aimed to assess the current PBM strategies in the Netherlands.

METHODS

An online electronic survey was developed and sent to surgeons of the Dutch Taskforce Coloproctology (177 in total). In addition, for each hospital in which surgery for colorectal cancer surgery is performed (75 in total), the survey was sent to one gastroenterologist and one anesthesiologist. Analyses were performed using descriptive statistics.

RESULTS

A total of 192 physicians responded to the survey (response rate 58.7%). In 73 hospitals (97.3%) the survey was conducted by at least one physician. Regarding the management of a mild‐moderate preoperative anemia, no clear policy was reported in half of the hospitals (49.3%). In 38.7% of the hospitals, iron status was indicated to be measured during screening for colorectal cancer. In addition, in only 13.3% of the hospitals, iron status was measured by the anesthesiologist during preoperative assessment.

CONCLUSION

The Present study shows a distinct variability in PBM practices in colorectal cancer care. Strikingly, this variability was not only seen between, but also within Dutch hospitals, demonstrated by often variable responses from physicians from the same institution. As a result, the present study clearly demonstrates the lack of consensus on PBM, resulting in a suboptimal preoperative blood management strategy.
Impact of collection programs for the generation of monocyte apheresis products on product quality and composition as starting material for the generation of cellular therapeutics
Authors: Pfeiffer Hella , Völkl Simon , Gary Regina , Mackensen Andreas , Achenbach Susanne , Strasser Erwin , Aigner Michael
Published: September 2018

BACKGROUND

With the discontinuation of the last generation of apheresis machines, new options for monocyte apheresis became available. As apheresis products play a crucial role in the generation of new cellular therapeutics (e.g., generation of dendritic cells [DCs] or precursor for T‐cell experiments) we sought to compare two different collection programs for potential benefits or disadvantages due to different composition of the cellular products.

STUDY DESIGN AND METHODS

Composition of discontinuously and continuously collected monocyte products from the same 13 donors was analyzed. For further evaluation as starting material for manufacturing of cellular therapeutics typically used steps such as Ficoll Isopaque, cryoconservation and monocyte isolation, with subsequent generation of mature DCs (mDCs) and assessment of T‐cell function, were performed on seven of these apheresis pairs.

RESULTS

Yield of total cells, monocytes, and mDCs was equal with both methods. T‐cell composition did not differ significantly in content of CD3+, CD4+, and CD8+ cells. Differentiation status and cytokine production of CD8+ T cells upon stimulation with cytomegalovirus pp65 antigen was not significantly different.

CONCLUSION

Both methods seem comparably suited for the generation of cellular products. If the intended use is “fresh” (without cryoconservation), continuously harvested cells show better cell numbers, while discontinuously harvested cells show better recovery after cryoconservation.
The effects of apheresis, storage time, and leukofiltration on microparticle formation in apheresis platelet products
Authors: Gao Ming , Zhang Bin , Zhang Yue , Chen Yuting , Xiong Jin , Wang Juan , Chen Hanwei , Chen Guoan , Wei Qing
Published: September 2018

BACKGROUND

Although platelet microparticles (PMPs) were the most abundant micoparticles (MPs) in platelet (PLT) products, other MPs and their parental cells can also be brought into the plasma during PLT apheresis. However, the effects of PLT apheresis, storage time, and leukofiltration on these MPs remain largely unclear.

STUDY DESIGN AND METHODS

Apheresis PLTs with or without leukofiltration were stored in 22 ± 2 °C for 5 days. PLT‐poor plasma (PPP) was generated by centrifugation of donor blood or PLT products at 2500 × g for 15 minutes on the point day. PPP was labeled with CD41a (PLT‐derived MP, PMP), CD235 (red blood cell–derived MP, RMP), CD45 (leukocyte‐derived MP, LMP), CD14 (monocyte‐derived MP, MMP), and CD144 (endothelial cell–derived MP, EMP), and then measured by flow cytometry.

RESULTS

Higher‐level TMPs (total microparticles) and PMPs, but lower‐level RMPs, LMPs, and MMPs were detected in fresh PLTs on the day of collection compared with those before collection. During storage, TMP, PMP, and RMP counts were significantly higher on Day 3 and Day 5, but MMP and LMP counts were only marginally higher on Day 3 in PLT supernatants. There were no significant differences in MP levels in PLTs with or without leukofiltration.

CONCLUSION

MP formation was affected by the apheresis procedure. RMPs, LMPs and MMPs were lower after PLT apheresis. During storage, TMPs, PMPs, RMPs, LMPs, and MMPs were found to be higher in PLT supernatants. Leukofiltration exerted no significant effect on all MPs in PLT products.
The accentedness, comprehensibility, and intelligibility of Asian Englishes
Authors: Hansen Edwards Jette G. , Zampini Mary L. , Cunningham Caitlin
Published: September 2018

This study examines the accentedness, comprehensibility, and intelligibility of speakers of English from China, Hong Kong, Singapore, and the United States (US) by listeners from Hong Kong, Singapore, China, and the US on two speech tasks (read vs. conversation). It also examines the effect of shared background on scores for all listeners as well as the effect of international experience for the Hong Kong and the US listeners. The study found that although accentedness and comprehensibility were positively correlated, neither variable was significantly correlated with intelligibility. The study found that shared background increased ratings of accentedness and comprehensibility but not intelligibility scores, and that international experience also had an effect during the conversational task, in that listeners with international experience received significantly higher intelligibility scores than those without any such international experience.
Adaptation of myocardial twist in the remodelled athlete's heart is not related to cardiac output
Authors: Cooke Samuel , Samuel T. Jake , Cooper Stephen‐Mark , Stöhr Eric J.
Published: September 2018

New Findings

What is the central question of this study?

What is the role of heart muscle function in the increased output of remodelled, larger hearts?

What is the main finding and its importance?

The greater stroke volume of endurance athletes is not associated with enhanced function of the heart muscle (i.e. left ventricular twist, torsion and twist‐to‐shortening) in normal and low‐oxygen environments. These data indicate that, in the process of cardiac adaptation, left ventricular twist may play an important role that is not related to generating a larger output. Since enlarged hearts with low output can develop in disease, the present findings may influence the future interpretation of heart muscle function in patients.

Despite increased stroke volume (SV), ‘athlete's heart’ has been proposed to have a similar left ventricular (LV) muscle function – as represented by LV twist – compared with the untrained state. However, the underpinning mechanisms and the associations between SV/cardiac output and LV twist during exercise are unknown. We hypothesised that endurance athletes would have a significantly lower twist‐to‐shortening ratio (TwSR, a parameter that relates twist to the shortening of heart muscle layers) at rest, but significantly greater LV muscle function during exercise. Eleven endurance trained male runners and 13 untrained males were tested at rest and during supine cycling exercise in normoxia and hypoxia (increased cardiac output but unaltered SV). Despite the expected cardiac remodelling in endurance athletes, LV twist, torsion, TwSR, strain and strain rate (‘LV systolic mechanics’) did not differ significantly between groups (P > 0.05). Structural remodelling, as per relative wall thickness, and LV twist did not correlate (r2 = 0.04, P = 0.33). In normoxia and hypoxia, exercise increased LV systolic mechanics in both groups (P < 0.001), but with different relationships to SV and cardiac output. Conversely to our hypothesis, hearts of different size had similar LV systolic mechanics, suggesting that similar twist, torsion and TwSR at rest and during exercise irrespective of cardiac output may be an important mechanism in healthy hearts. We hypothesise that the regulatory ‘purpose’ of LV twist may be related to the sensing of maximal cardiac myofibre stress, which may act as a biologically purposeful limiter to contraction.
Stealing Thunder Through Social Media: The Framing of Maria Sharapova’s Drug Suspension
Authors: Bell Travis R. , Hartman Karen L.
Published: September 2018

In March 2016 the highest-paid women’s athlete, Maria Sharapova, called a press conference to announce a failed drug test. Sharapova relied on the crisis communication strategy of stealing thunder to present the information to media and break the story. The authors analyze how the press conference and her strategy were portrayed in traditional and online media and how Sharapova promoted and broadcast the press conference to defend herself. Using Linguistic Inquiry and Word Count (LIWC) software and textual analysis, the authors argue that Sharapova’s use of the stealing-thunder strategy successfully influenced media narratives about her suspension and should be considered by athletes in crisis situations.
The Influence of Pleasure and Attentional Focus on Performance and Pacing Strategies in Elite Individual Time Trials
Authors: Ouvrard Theo , Groslambert Alain , Grappe Frederic
Published: September 2018

Recent psychophysiological models of endurance performance explained that pacing strategies and exercise-intensity regulation influence cyclists’ ability to produce high mean power output (PO) during time trials (TTs). However, the relationships between these pacing strategies and psychological parameters of the athletes remain unknown. Purpose: To determine the impact of pacing strategies on cyclists’ mean PO during an elite TT championship and to identify the relationships between these pacing strategies and psychological parameters. Methods: Mean PO, projected frontal area, attentional focus, and pleasure were recorded for 9 male cyclists during an official individual TT national championship. Pacing regulations were quantified from PO using the new exposure variation analysis, which determines times spent at adapted PO for optimal constant-pacing strategy (APO) and inaccurate PO for optimal constant-pacing strategy (IPO). Relationships between mean PO, times spent at APO and IPO, and psychological variables were analyzed. Results: Significant relationships were found between mean PO and exposure variation analysis pacing parameters (r2 .56–.86, P > .05). Time spent at IPO was negatively related to pleasure during the individual TT (r = −.746, P = .016). Conversely, time spent at APO was significantly related to cyclists’ attentional focus (r = .827, P = .006). Conclusions: Mean PO during elite individual TTs is directly related to athletes’ ability to optimally regulate pace throughout the event. This pacing regulation is influenced by attentional focus and pleasure, underlining that coaches and athletes should devote greater attention to these psychological parameters to improve their performances.
The Reproducibility and External Validity of a Modified Rugby League Movement-Simulation Protocol for Interchange Players
Authors: Norris Jonathan P. , Highton Jamie , Twist Craig
Published: September 2018

Purpose: To assess the reliability and external validity of a rugby league movement-simulation protocol for interchange players (RLMSP-i) that was adapted to include physical contact between participants. Methods: A total of 18 rugby players performed 2 trials of a modified RLMSP-i, 7 d apart. The simulation was conducted outdoors on artificial turf with movement speeds controlled using an audio signal. Microtechnology was used to measure locomotive and accelerometer (ie, PlayerLoad™) metrics for both bouts (∼23 min each) alongside heart rate (HR) and rating of perceived exertion (RPE). Results: Reported for each bout, total distance (102 [3] m·min−1 and 101 [3] m·min−1), low-speed distance (77 [3] m·min−1 and 79 [4] m·min−1), high-speed distance (25 [3] m·min−1 and 22 [4] m·min−1), PlayerLoad (10 [1] AU·min−1 and 10 [1] AU·min−1), PlayerLoad slow (3.2 [0.6] AU·min−1 and 3.2 [0.6] AU·min−1), 2-dimensional PlayerLoad (6.0 [0.9] AU·min−1 and 5.7 [0.8] AU·min−1), and HR (86 [5]%HRmax and 84 [6]%HRmax) were similar to match play. The coefficient of variation (CV%) for locomotive metrics ranged from 1.3% to 14.4%, accelerometer CV% 4.4% to 10.0%, and internal load 4.8% to 13.7%. All variables presented a CV% less than the calculated moderate change during 1 or both bouts of the simulation except high-speed distance, percentage of the participant’s peak HR, and RPE. Conclusion: The modified RLMSP-i offers a reliable simulation to investigate influences of training and nutrition interventions on the movement and collision activities of rugby league interchange players.
Caffeine and Sprint Cycling Performance: Effects of Torque Factor and Sprint Duration
Authors: Glaister Mark , Towey Colin , Jeffries Owen , Muniz-Pumares Daniel , Foley Paul , McInnes Gillian
Published: September 2018

Purpose: To investigate the influence of torque factor and sprint duration on the effects of caffeine on sprint cycling performance. Methods: Using a counterbalanced, randomized, double-blind, placebo-controlled design, 13 men completed 9 trials. In trial 1, participants completed a series of 6-s sprints at increasing torque factors to determine the torque factor, for each individual, that elicited the highest (Toptimal) peak power output (PPO). The remaining trials involved all combinations of torque factor (0.8 N·m−1·kg−1 vs Toptimal), sprint duration (10 s vs 30 s), and supplementation (caffeine [5 mg·kg−1] vs placebo). Results: There was a significant effect of torque factor on PPO, with higher values at Toptimal (mean difference 168 W; 95% likely range 142–195 W). There was also a significant effect of sprint duration on PPO, with higher values in 10-s sprints (mean difference 52 W; 95% likely range 18–86 W). However, there was no effect of supplementation on PPO (P = .056). Nevertheless, there was a significant torque factor × sprint duration × supplement interaction (P = .036), with post hoc tests revealing that caffeine produced a higher PPO (mean difference 76 W; 95% likely range 19–133 W) when the sprint duration was 10 s and the torque factor was Toptimal. Conclusion: The results of this study show that when torque factor and sprint duration are optimized, to allow participants to express their highest PPO, there is a clear effect of caffeine on sprinting performance.
Deficits in Planning Sequential Goal-Directed Action Impact Motor Execution in Children With Hemiplegic Cerebral Palsy: A Kinematic Analysis
Authors: Surkar Swati M. , Hoffman Rashelle M. , Davies Brenda , Harbourne Regina , Kurz Max J.
Published: September 2018

There is mounting experimental evidence that suggests children with hemiplegic cerebral palsy (HCP) lack the ability to properly plan their motor actions. The purpose of this investigation was to determine how these planning deficits might affect the ability of children with HCP to execute a complex sequence of actions that have different final end states in the hand/arm position. Thirteen children with HCP (age = 6.8 ± 2.9 yrs, Manual Ability Classification levels = II–IV) and 15 typically developing (TD) children (age = 5.8 ± 1.1 yrs) completed a sequential motor task that involved reaching to grasp an object and place it into six-different target positions. Each target had a biomechanically different final hand/arm position for placing the object. A three-dimensional motion capture system was used to calculate the resultant spatiotemporal kinematics of a marker that was placed on the hand. In addition, video analysis was used to quantify the child’s reaction time, end-state comfort effect, and task failures. Compared with the TD children, the children with HCP had notable deviations in their spatiotemporal kinematics when reaching for the object and placing it in the respective target positions. The children with HCP also exhibited slower reaction time, reduced end-state comfort, and increased number of task failures when placing the objects in the respective target potions. Interestingly, the children with HCP showed impaired planning on the affected as well as the less affected arm. This suggests that the inability of children with HCP to properly plan a motor action might partly arise from central deficits in their cognitive processing, and not exclusively from the peripheral deficits seen in the musculoskeletal system. Altogether our results imply that children with HCP lack the ability to plan and execute sequential motor actions.
Developmental phosphoproteomics identifies the kinase CK2 as a driver of Hedgehog signaling and a therapeutic target in medulloblastoma
Authors: Purzner Teresa , Purzner James , Buckstaff Taylor , Cozza Giorgio , Gholamin Sharareh , Rusert Jessica M. , Hartl Tom A. , Sanders John , Conley Nicholas , Ge Xuecai , Langan Marc , Ramaswamy Vijay , Ellis Lauren , Litzenburger Ulrike , Bolin Sara , Theruvath Johanna , Nitta Ryan , Qi Lin , Li Xiao-Nan , Li Gordon , Taylor Michael D. , Wechsler-Reya Robert J. , Pinna Lorenzo A. , Cho Yoon-Jae , Fuller Margaret T. , Elias Joshua E. , Scott Matthew P.
Published: September 2018

Inhibitors of the kinase CK2 may halt the growth of an aggressive form of medulloblastoma.
Engineering Pseudochelin Production in Myxococcus xanthus
Authors: Korp Juliane , Winand Lea , Sester Angela , Nett Markus
Published: September 2018

In this study, an enzyme for imidazoline formation in pseudochelin biosynthesis was identified. Evidence for the involvement of this enzyme in the postulated reaction was obtained after
in vitro
reconstitution. Furthermore, the function of this enzyme was demonstrated
in vivo
by transferring the corresponding gene into the bacterium
Myxococcus xanthus
, which thereby became a producer of pseudochelin A. In addition to clarifying the molecular basis of imidazoline formation in siderophore biosynthesis, we describe the heterologous expression of a gene in a myxobacterium without chromosomal integration. Due to its metabolic proficiency,
M. xanthus
represents an interesting alternative to established host systems for the reconstitution and manipulation of biosynthetic pathways. Since the plasmid used in this study is easily adaptable for the expression of other enzymes as well, we expand the conventional expression strategy for myxobacteria, which is based on the integration of biosynthetic genes into the host genome.
Regulatory Networks Governing Methionine Catabolism into Volatile Organic Sulfur-Containing Compounds in Clonostachys
rosea
Authors: Xu Yang-Hua , Jia Kai-Zhi , Tang Ya-Jie
Published: September 2018

Methionine shuttles organic nitrogen and plays a central role in nitrogen metabolism. Exogenous Met strongly induces the expression of
ARO8-2
and
PDC
, represses the expression of
STR3
, and generates volatile organic sulfur-containing compounds via the Ehrlich and demethiolation pathways. In this study, we used genetic, bioinformatic, and metabolite-based analyses to confirm that transcriptional control of the aminotransferase gene
ARO8-2
, the decarboxylase gene
PDC
, and the demethiolase gene
STR3
modulates Met catabolism into volatile organic sulfur-containing compounds. Importantly, we found that, in addition to the Ehrlich pathway, the demethiolation pathway was regulated by a nitrogen catabolite repression-sensitive regulatory pathway that controlled the transcription of genes required to catabolize poor nitrogen sources. This work significantly advances our understanding of nitrogen catabolite repression-sensitive transcriptional regulation of sulfur-containing amino acid catabolism and provides a basis for engineering Met catabolism pathways for the production of fuel and valuable flavor alcohols.
Limited Pulmonary Mucosal-Associated Invariant T Cell Accumulation and Activation during Mycobacterium tuberculosis Infection in Rhesus Macaques
Authors: Kauffman Keith D. , Sallin Michelle A. , Hoft Stella G. , Sakai Shunsuke , Moore Rashida , Wilder-Kofie Temeri , Moore Ian N. , Sette Alessandro , Arlehamn Cecilia S. Lindestam , Barber Daniel L.
Published: September 2018

Mucosal-associated invariant T cells (MAITs) are positioned in airways and may be important in the pulmonary cellular immune response againstMycobacterium tuberculosisinfection, particularly prior to priming of peptide-specific T cells. Accordingly, there is interest in the possibility that boosting MAITs through tuberculosis (TB) vaccination may enhance protection, but MAIT responses in the lungs during tuberculosis are poorly understood.
Multiple Flagellin Proteins Have Distinct and Synergistic Roles in Agrobacterium tumefaciens Motility
Authors: Mohari Bitan , Thompson Melene A. , Trinidad Jonathan C. , Setayeshgar Sima , Fuqua Clay
Published: September 2018

Flagellins are abundant bacterial proteins comprising the flagellar filaments that propel bacterial movement. Several members of the alphaproteobacterial group express multiple flagellins, in contrast to model systems, such as with
Escherichia coli
, which has one type of flagellin. The plant pathogen
Agrobacterium tumefaciens
has four flagellins, the abundant and readily detected FlaA and FlaB, and lower levels of FlaC and FlaD. Mutational analysis reveals that FlaA requires at least one of the other flagellins to function, as
flaA
mutants produce nonhelical flagella and cannot swim efficiently. Suppressor mutations can rescue this swimming defect through mutations in the remaining flagellins, including structural changes imparting helical shape to the flagella, and putative regulators. Our findings shed light on how multiple flagellins contribute to motility.
Epstein-Barr Virus MicroRNA miR-BART5-3p Inhibits p53 Expression
Authors: Zheng Xiang , Wang Jia , Wei Lingyu , Peng Qiu , Gao Yingxue , Fu Yuxin , Lu Yuanjun , Qin Zailong , Zhang Xuemei , Lu Jianhong , Ou Chunlin , Li Zhengshuo , Zhang Xiaoyue , Liu Peishan , Xiong Wei , Li Guiyuan , Yan Qun , Ma Jian
Published: September 2018

EBV encodes 44 mature microRNAs, which have been proven to promote EBV-associated diseases by targeting host genes and self-viral genes. In EBV-associated carcinomas, the expression of viral protein is limited but the expression of BART microRNAs is extremely high, suggesting that they could be major factors in the contribution of EBV-associated tumorigenesis. p53 is a critical tumor suppressor. Unlike in most human solid tumors, TP53 mutations are rare in nasopharyngeal carcinoma and EBV-associated gastric carcinoma tissues, suggesting a possibility that some EBV-encoded products suppress the functions of p53. This study provides the first evidence that a BART microRNA can suppress p53 expression by directly targeting its 3′-UTR. This study implies that EBV can use its BART microRNAs to modulate the expression of p53, thus maintaining its latency and contributing to tumorigenesis.
A Single Point Mutation in the Rhinovirus 2B Protein Reduces the Requirement for Phosphatidylinositol 4-Kinase Class III Beta in Viral Replication
Authors: Roulin Pascal S. , Murer Luca P. , Greber Urs F.
Published: September 2018

Human rhinoviruses (RVs) are the major cause of the common cold worldwide. They cause asthmatic exacerbations and chronic obstructive pulmonary disease. Despite recent advances, the development of antivirals and vaccines has proven difficult due to the high number and variability of RV types. The identification of critical host factors and their interactions with viral proteins and membrane lipids for the establishment of viral replication is a basis for drug development strategies. Our findings here shed new light on the interactions between nonstructural viral membrane proteins and class III phosphatidylinositol 4 kinases from the host and highlight the importance of phosphatidylinositol 4 phosphate for RV replication.
Cytosolic Recognition of Microbes and Pathogens: Inflammasomes in Action
Authors: Hayward Jenni A. , Mathur Anukriti , Ngo Chinh , Man Si Ming
Published: September 2018

Infection is a dynamic biological process underpinned by a complex interplay between the pathogen and the host. Microbes from all domains of life, including bacteria, viruses, fungi, and protozoan parasites, have the capacity to cause infection.
Interplay between Peptidoglycan Biology and Virulence in Gram-Negative Pathogens
Authors: Juan Carlos , Torrens Gabriel , Barceló Isabel Maria , Oliver Antonio
Published: September 2018

The clinical and epidemiological threat of the growing antimicrobial resistance in Gram-negative pathogens, particularly for β-lactams, the most frequently used and relevant antibiotics, urges research to find new therapeutic weapons to combat the infections caused by these microorganisms. An essential previous step in the development of these therapeutic solutions is to identify their potential targets in the biology of the pathogen.
Clinical profile, risk factors and outcome of medical, surgical and adjunct interventions in patients with
Pythium
insidiosum
keratitis
Authors: Agarwal Shweta , Iyer Geetha , Srinivasan Bhaskar , Benurwar Saket , Agarwal Mamta , Narayanan Niveditha , Lakshmipathy Meena , Radhika N , Rajagopal Rama , Krishnakumar S , K Lily Therese
Published: September 2018

Purpose

To report clinical profile and compare management options for Pythium keratitis.

Method

Retrospective interventional study of 46 patients diagnosed as Pythium keratitis by PCR DNA sequencing from January 2014 to July 2017. Interventions were categorised into medical management (MM) (topical azithromycin and linezolid with oral azithromycin at presentation), surgery (S) (therapeutic penetrating keratoplasty, TPK), surgical adjunct (SA) (cryotherapy±alcohol with TPK) and medical adjunct (MA) (MM after TPK).

Results

Primary treatment included MM (1 eye), SA (3 eyes) and S (42 eyes). Recurrence occurred in 27/43 eyes (MM+S group). Second surgery (S) was required in 11 eyes (TPK-2), with additional procedures (SA) in 10 eyes and evisceration in five eyes. 8/43 eyes received MA after TPK-1. One eye required TPK-3. Recurrence occured in all eyes that received MA (100%) and in 28 of 54 TPKs (51.8%) (TPK 1+2+3) in 42 eyes. Recurrence was noted in 1/14 (7.1%) that underwent SA.

Conclusion

The currently available and recommended treatment for Pythium keratitis is surgical by means of a TPK and in worse cases evisceration. In our study, MM/MA measures showed no benefit with recurrence or worsening of infection requiring resurgery. Almost 50% of TPKs had a recurrence requiring resurgery. However, adjunctive procedures during TPK appear to have additional benefit with low risk of recurrence and could be included as routine care.
Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour
Authors: Zhang Jianrong , Zhang Yiyin , Tang Shiyan , Jiang Long , He Qihua , Hamblin Lindsey Tristine , He Jiaxi , Xu Zhiheng , Wu Jieyu , Chen Yaoqi , Liang Hengrui , Chen Difei , Huang Yu , Wang Xinyu , Deng Kexin , Jiang Shuhan , Zhou Jiaqing , Xu Jiaxuan , Chen Xuanzuo , Liang Wenhua , He Jianxing
Published: September 2018

Objective

Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.

Design

Literature review, pooling analysis and correlation analysis.

Data sources

PubMed, from 1 January 2010 to 30 June 2017.

Eligibility criteria for selecting studies

Eligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments.

Results

Of 76 included trials involving 45 688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29).

Conclusions

No systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.
Strategies to improve adherence to antiretroviral therapy and retention in care for people living with HIV in high-income countries: a protocol for an overview of systematic reviews
Authors: Mbuagbaw Lawrence , Mertz Dominik , Lawson Daeria O , Smieja Marek , Benoit Anita C , Alvarez Elizabeth , Puchalski Ritchie Lisa , Rachlis Beth , Logie Carmen , Husbands Winston , Margolese Shari , Thabane Lehana
Published: September 2018

Introduction

While access to antiretroviral therapy (ART) for people living with HIV has expanded in recent years, additional efforts are required to support adherence to medication and retention in care. Interventions should be applicable in real-world settings and amenable to widespread use. The objectives of this overview are to identify effective pragmatic interventions that increase adherence to ART and retention in care for people living with HIV at high risk for suboptimal adherence and retention in high-income countries.

Methods and analysis

We will conduct an overview of systematic reviews of studies on interventions which target improved adherence to medication and retention in care among high-risk people living with HIV in high-income countries (men who have sex with men, African, Caribbean and black people, sex workers, people who inject drugs, indigenous people and other socially marginalised groups). We will search the following databases: PubMed, EMBASE (Exerpta Medica Database), CINAHL (Cumulative Index to Nursing and Allied Health Literature), PsycINFO, Web of Science and the Cochrane Library. We will conduct screening, data extraction and assessment of methodological quality of the systematic reviews. Analysis will be narrative. Our findings will be interpreted in light of the certainty of the evidence, level of pragmatism, setting and population of interest.

Ethics and dissemination

Only published secondary data will be used in this study, and therefore ethics approval is not required. Our findings will be disseminated as peer-reviewed manuscripts, conference abstracts and through community activities. The findings from this overview will inform a mixed-methods study among people living with HIV and health workers in Ontario, Canada.
Pulse wave reflection responses to bench press with and without practical blood flow restriction
Authors: Tai Yu Lun , Marshall Erica M. , Glasgow Alaina , Parks Jason C. , Sensibello Leslie , Kingsley J. Derek
Published: September 2018

Resistance exercise is recommended to increase muscular strength but may also increase pulse wave reflection. The effect of resistance exercise combined with practical blood flow restriction (pBFR) on pulse wave reflection is unknown. The purpose of this study was to evaluate the differences in pulse wave reflection characteristics between bench press with pBFR and traditional high-load bench press in resistance-trained men. Sixteen resistance-trained men participated in the study. Pulse wave reflection characteristics were assessed before and after low-load bench press with pBFR (LL-pBFR), traditional high-load bench press (HL), and a control (CON). A repeated-measures ANOVA was used to evaluate differences in pulse wave reflection characteristics among the conditions across time. There were significant (p ≤ 0.05) interactions for heart rate, augmentation index, augmentation index normalized at 75 bpm, augmentation pressure, time–tension index, and wasted left ventricular energy such that they were increased after LL-pBFR and HL compared with rest and CON, with no differences between LL-pBFR and HL. Aortic pulse pressure (p < 0.001) was elevated only after LL-pBFR compared with rest. In addition, there was a significant (p ≤ 0.05) interaction for aortic diastolic blood pressure (BP) such that it was decreased after LL-pBFR compared with rest and CON but not HL. The subendocardial viability ratio and diastolic pressure–time index were significantly different between LL-pBFR and HL compared with rest and CON. There were no significant interactions for brachial systolic or diastolic BP, aortic systolic BP, or time of the reflected wave. In conclusion, acute bench press resistance exercise significantly altered pulse wave reflection characteristics without differences between LL-pBFR and HL.
Standardized ileal digestible amino acids and apparent metabolizable energy content in defatted black soldier fly larvae meal fed to broiler chickens
Authors: Mwaniki Z.N. , Kiarie E.
Published: September 2018

Standardized ileal digestibility (SID) of amino acids (AA) and apparent metabolizable energy corrected for nitrogen (AMEn) in defatted black soldier fly larvae meal (BSFLM) were determined in broiler chicks. A total of 180-d-old male broiler chicks (Ross 708) were fed a commercial broiler starter diet to day 13 of age. On day 14, birds were weighed and placed in cages (10 birds per cage; n = 6) and allocated one of two semi-purified cornstarch-based diets. The diets were nitrogen-free diet (NFD) for estimating endogenous AA losses and 20% crude protein test diet with BSFLM as the sole source of AA. All diets had 0.5% titanium dioxide (TiO2) as an indigestible marker and the ratio of cornstarch to sucrose and soy oil in the test diet was identical to NFD to calculate AMEn by difference method. Birds were given feed and water ad libitum. Excreta samples were collected on days 17–20 and ileal digesta on day 21. The SID of lysine, methionine, cysteine, threonine, isoleucine, and valine was 86.3%, 88.7%, 72.8%, 85.5%, 89.6%, and 88.6%, respectively. Apparent retention of gross energy in BSFLM was 64.5% ± 2.27% and AMEn was 2902 ± 101 kcal kg−1 dry matter. The data will aid in accurate incorporation of BSFLM in poultry feeding programs.
Multidisciplinary approaches for studying rhizobium–legume symbioses
Authors: diCenzo George C. , Zamani Maryam , Checcucci Alice , Fondi Marco , Griffitts Joel S. , Finan Turlough M. , Mengoni Alessio
Published: September 2018

The rhizobium–legume symbiosis is a major source of fixed nitrogen (ammonia) in the biosphere. The potential for this process to increase agricultural yield while reducing the reliance on nitrogen-based fertilizers has generated interest in understanding and manipulating this process. For decades, rhizobium research has benefited from the use of leading techniques from a very broad set of fields, including population genetics, molecular genetics, genomics, and systems biology. In this review, we summarize many of the research strategies that have been employed in the study of rhizobia and the unique knowledge gained from these diverse tools, with a focus on genome- and systems-level approaches. We then describe ongoing synthetic biology approaches aimed at improving existing symbioses or engineering completely new symbiotic interactions. The review concludes with our perspective of the future directions and challenges of the field, with an emphasis on how the application of a multidisciplinary approach and the development of new methods will be necessary to ensure successful biotechnological manipulation of the symbiosis.
Effects of territorial status and life history on Sandhill Crane (Antigone canadensis) population dynamics in south-central Wisconsin, USA
Authors: Wheeler Michael E. , Barzen Jeb A. , Crimmins Shawn M. , Van Deelen Timothy R.
Published: September 2018

Population growth rate in long-lived bird species is often most sensitive to changes in adult survival. Sandhill Cranes (Antigone canadensis (Linnaeus, 1758)) have long life spans, small broods, and delayed first reproduction. Only territorial adult Sandhill Cranes participate in breeding, and territory acquisition reflects the interplay between the availability of suitable territories and the variation in mortality of adult birds occupying those territories. We estimated vital rates of a population at equilibrium using long-term resightings data (2000–2014; n = 451 marked individuals) in a multistate mark–resight model and used a stage-structured projection matrix to assess how strongly territorial adult survival affects population growth rate. Elasticity analysis indicated territorial birds surviving and retaining territories had a 2.58 times greater impact on population growth compared with the next most important transition rate (survival of nonterritorial adults remaining nonterritorial). Knowing how changes in vital rates of various stage classes will differentially impact population growth rate allows for targeted management actions including encouraging growth in recovering populations, assessing opportunity for recreational harvest, or maintaining populations at a desired level. This study also highlights the value of collecting demographic data for all population segments, from which one can derive reproductive output or growth rate.