bluuebunny/crossref_metadata_2025 huggingface dataset:
Microsurgical Breast Reconstruction in the Obese: A Better Option Than Tissue Expander/Implant Reconstruction?
Authors: Klement Kristen A. , Hijjawi John B. , LoGiudice John A. , Alghoul Mohammad , Omesiete-Adejare Pamela
Published: August 2019

Background:

Obesity has reached epidemic proportions, with 72 million people in the United States classified as obese in 2010. This significant increase in obese patients is reflected in the breast cancer population seeking breast reconstruction. Previous studies demonstrated increased complication rates and decreased satisfaction in obese patients undergoing breast reconstruction. This study aims to directly compare prosthetic and autologous reconstruction in the obese population by evaluating surgical outcomes and patient satisfaction.

Methods:

In an institutional review board–approved study, a retrospective chart review was conducted on patients with a body mass index of 30.0 kg/m2 or greater who underwent breast cancer reconstruction after mastectomy with either free tissue transfer from the abdomen or prosthetic reconstruction over a 3-year period. The authors identified 96 patients with 141 reconstructions. Demographic, intraoperative, and postoperative variables were collected. All patients were sent the BREAST-Q questionnaire by means of mail to study the impact and effectiveness of breast surgery from the patient’s perspective. Statistical analysis was completed with Fisher’s exact test, Mantel-Haenszel chi-square test, Pearson chi square test, or Mann-Whitney-Wilcoxon test.

Results:

Prosthetic-based breast reconstruction was associated with increased major breast complications (p < 0.001), mastectomy skin flap necrosis (p = 0.009), infection (0.006), and overall reconstructive failure (p < 0.0001) compared with autologous reconstruction. When evaluating the results of the BREAST-Q studies, the autologous reconstruction group had improved satisfaction with breasts (p < 0.0001), satisfaction with outcome (p = 0.01), psychosocial well-being (p = 0.007), and sexual well-being (p = 0.006).

Conclusion:

In the obese population, reconstruction with free tissue transfer from the abdomen resulted in decreased complications of the breast reconstruction site and improved patient satisfaction with outcomes compared with prosthetic reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Absorbable Fixation Devices for Pediatric Craniomaxillofacial Trauma: A Systematic Review of the Literature
Authors: Lopez Joseph , Siegel Nicholas , Reategui Alvaro , Faateh Muhammad , Manson Paul N. , Redett Richard J.
Published: August 2019

Background:

The purpose of this study was to investigate surgical outcomes with the use of resorbable plating systems for the repair of craniomaxillofacial trauma in the pediatric population.

Methods:

A systematic review of the literature was performed. A descriptive analysis, operative technical data, outcomes, and postoperative complications with the use of absorbable plating systems for craniomaxillofacial trauma were included.

Results:

The systematic literature review identified 1264 abstracts, of which only 19 met inclusion criteria. From these 19 studies, 312 clinical cases with 443 facial fractures that were treated with absorbable fixation systems were extracted for analysis. The review identified only level III/IV (n = 17) and level V (n = 2) studies. Minor and major complications were rare, occurring in 5.45 percent (n = 17) and 3.21 percent (n = 10) of cases, respectively. The most common complications were surgical-site infections (n = 4) and plate extrusion (n = 4).

Conclusions:

This report is, to the authors’ knowledge, one of the first comprehensive reports on the use of absorbable plating systems for pediatric craniomaxillofacial trauma. Their analysis suggests that the use of absorbable fixation devices for pediatric craniomaxillofacial trauma is relatively safe, with a low-risk profile. Outcome studies with longer follow-up periods specifically investigating facial growth, reoperation rates, standardized surgical outcome metrics, and cost are necessary to effectively compare these fixation devices to titanium alternatives for craniomaxillofacial trauma.
Flap Blood Glucose as a Sensitive and Specific Indicator for Flap Venous Congestion: A Rodent Model Study
Authors: Mochizuki Kana , Mochizuki Masato , Gonda Koichi
Published: August 2019

Background:

Flap blood glucose decreases when flap congestion occurs. The hypothesis that flap blood glucose works as an indicator for venous congestion was tested experimentally, and flap congestion was reproduced in rodent models.

Methods:

Blood glucose levels of a rat abdominal skin flap, with or without its vein pedicle clamped, were checked before and every 10 minutes after flap elevation. In rats whose pedicle vein was shut off, it was further followed up every 5 minutes after declamping. To examine the effect of systemic blood glucose on flap blood glucose, in some rats, glucose solution was administered intraperitoneally before the experiment to artificially produce hyperglycemia. Forty-two rats were divided into four groups, with (n = 24) or without (n = 18) venous blockage and with (n = 20) or without (n = 22) glucose preloading.

Results:

Flap blood glucose decreased rapidly to off-scale low (<20 mg/dl) within 40 minutes only when the vein pedicle was shut off in normoglycemic (40 ± 8.2 minutes, mean ± SD) and hyperglycemic (40 ± 9.9 minutes) rat groups (p < 0.01). There was no significant difference in the time taken for the flap blood glucose to decrease to off-scale low after venous blockage between both groups (p = 0.379). When the vein was declamped, flap blood glucose again rapidly returned to the systemic level in 15 minutes or earlier in both groups (p = 0.0283).

Conclusions:

Flap blood glucose sensitively and specifically reflects the state of vein occlusion, whether the systemic blood glucose is normal or high. The authors’ results indicate that flap blood glucose works as a reliable indicator for the venous system.
Replantation of Cryopreserved Fingers: An “Organ Banking” Breakthrough
Authors: Wang Zengtao , Zhu Lei , Kou Wei , Sun Wenhai , He Bo , Wang Chunxia , Shen Yun , Wang Yang , Zhu Zhaowei , Liang You
Published: August 2019

Background:

Although cryopreservation has been widely used in clinical practice, it remains limited to small or thin bloodless tissues with a simple structure and function. In August of 2002, the authors performed the first successful transplantation of a cryopreserved vascularized rat hind limb. Subsequently, the authors extended this cryopreservation technique to the preservation of human fingers.

Methods:

In December of 2002 and December of 2003, the authors performed two in situ implantations of cryopreserved amputated fingers for two patients by means of the “two-step” and programmed cryopreservation methods. In case 1, computed tomographic angiography was performed on the affected hand 6 months after surgery. In case 2, pieces of skin were obtained from the thawed amputated finger for pathologic examination before replantation.

Results:

One finger was cryopreserved for 81 days and the other for 5 days. Both fingers were replanted successfully. Computed tomographic angiography revealed a patent radial proper digital artery in case 1. The pathologic results of case 2 showed satisfactory skin cell morphology. After 15- and 14-year follow-up assessments of the two patients, the replanted fingers achieved satisfactory appearance and function.

Conclusions:

The authors confirmed the effectiveness of deep cryopreservation for the long-term preservation of human fingers. The current application scope of these cryopreservation techniques includes small limbs with minimal amounts of muscle tissue.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, V.
Adenosine 5’-Monophosphate Protects from Hypoxia by Lowering Mitochondrial Metabolism and Oxygen Demand
Authors: Kondo Yutaka , Sueyoshi Koichiro , Zhang Jingping , Bao Yi , Li Xiaoou , Fakhari Mahtab , Slubowski Christian J. , Bahrami Soheyl , Ledderose Carola , Junger Wolfgang G.
Published: August 2019

Ischemia and reperfusion injury following severe trauma or cardiac arrest are major causes of organ damage in intensive care patients. The brain is particularly vulnerable because hypoxia rapidly damages neurons due to their heavy reliance on oxidative phosphorylation. Therapeutic hypothermia can reduce ischemia-induced brain damage, but cooling procedures are slow and technically difficult to perform in critical care settings. It has been previously reported that injection of naturally occurring adenosine 5’-monophosphate (AMP) can rapidly induce hypothermia in mice. We studied the underlying mechanisms and found that AMP transiently reduces the heart rate, respiratory rate, body temperature, and the consciousness of adult male and female C57BL/6J mice. Adding AMP to mouse or human neuronal cell cultures dose-dependently reduced the membrane potential (ΔΨm) and Ca2+ signaling of mitochondria in these cells. AMP treatment increased intracellular AMP levels and activated AMP-activated protein kinase, which resulted in the inhibition of mammalian target of rapamycin complex 1 (mTORC1) and of mitochondrial and cytosolic Ca2+ signaling in resting and stimulated neurons. Pretreatment with an intraperitoneal injection of AMP almost doubled the survival time of mice under hypoxic (6% O2) or anoxic (<1% O2) conditions when compared to untreated mice. These findings suggest that AMP induces a hypometabolic state that slows mitochondrial respiration, reduces oxygen demand, and delays the processes that damage mitochondria in the brain and other organs following hypoxia and reperfusion. Further examination of these mechanisms may lead to new treatments that preserve organ function in critical care patients.
Variation in Intraoperative and Postoperative Utilization for 3 Common General Surgery Procedures
Authors: Childers Christopher P. , Ettner Susan L. , Hays Ron D. , Kominski Gerald , Maggard-Gibbons Melinda , Alban Rodrigo F.
Published: August 2019

Objective:

The aim of this study was to understand variation in intraoperative and postoperative utilization for common general surgery procedures.

Summary Background Data:

Reducing surgical costs is paramount to the viability of hospitals.

Methods:

Retrospective analysis of electronic health record data for 7762 operations from 2 health systems. Adult patients undergoing laparoscopic cholecystectomy, appendectomy, and inguinal/femoral hernia repair between November 1, 2013 and November 30, 2017 were reviewed for 3 utilization measures: intraoperative disposable supply costs, procedure time, and postoperative length of stay (LOS). Crossed hierarchical regression models were fit to understand case-mixed adjusted variation in utilization across surgeons and locations and to rank surgeons.

Results:

The number of surgeons performing each type of operation ranged from 20 to 63. The variation explained by surgeons ranged from 8.9% to 38.2% for supply costs, from 15.1% to 54.6% for procedure time, and from 1.3% to 7.0% for postoperative LOS. The variation explained by location ranged from 12.1% to 26.3% for supply costs, from 0.2% to 2.5% for procedure time, and from 0.0% to 31.8% for postoperative LOS. There was a positive correlation (ρ = 0.49, P = 0.03) between surgeons’ higher supply costs and longer procedure times for hernia repair, but there was no correlation between other utilization measures for hernia repair and no correlation between any of the utilization measures for laparoscopic appendectomy or cholecystectomy.

Conclusions:

Surgeons are significant drivers of variation in surgical supply costs and procedure time, but much less so for postoperative LOS. Intraoperative and postoperative utilization profiles can be generated for individual surgeons and may be an important tool for reducing surgical costs.
Casting A Wide Net On Surgery
Authors: Eustache Jules H. , Tohme Samer , Milette Simon , Rayes Roni F. , Tsung Allan , Spicer Jonathan D.
Published: August 2019

Since their discovery, neutrophil extracellular traps (NETs) have been implicated in a broad array of functions, both beneficial and detrimental to the host. Indeed, NETs have roles in infection, sepsis, wound healing, thrombotic disease, and cancer propagation, all of which are directly implicated in the care of surgical patients. Here we provide an updated review on the role of NETs in the perioperative period with specific emphasis on perioperative infections, wound healing, vascular complications, cancer propagation, as well as discussing ongoing, and future therapeutic targets. Surgeons will benefit from understanding the latest discoveries in neutrophil biology and how these novel functions affect the care of surgical patients. Furthermore, novel anti-NET therapies are being developed which may have profound effects on the care of surgical patients.
Frontotemporal Dementia Knowledge Scale
Authors: Wynn Matthew J. , Carpenter Brian D.
Published: August 2019

Objective:

Frontotemporal dementia (FTD) accounts for ∼10% of dementia cases and is the most common cause of early-onset dementia. However, no well-validated instrument currently exists to measure knowledge about FTD. In this study, we used systematic scale development procedures to create a scale to measure knowledge of FTD based on a contemporary understanding of the disease.

Methods:

Standard scale development methods were used to create items and evaluate their psychometric properties. A total of 72 health care professionals and 102 caregivers of people with FTD responded to items measuring FTD knowledge, general dementia knowledge, crystallized intelligence, experience with FTD, and demographic information.

Results:

The Frontotemporal Dementia Knowledge Scale (FTDKS) contains 18 items that cover key, basic knowledge about FTD in the domains of risk factors, symptoms, course, caregiving, and treatment. The scale uses a 4-point True/False format with a Don’t Know option and takes ∼5 minutes to complete. In the current sample the FTDKS had good psychometric properties in terms of reliability and validity.

Implications:

The FTDKS can be used with health care professionals and caregivers of people with FTD to assess their knowledge about the disease. The scale may be useful to evaluate knowledge in clinical care and educational program contexts.
Effect of Ostomy Care Team Intervention on Patients With Ileal Conduit
Authors: Zhou Haiyan , Ye Yufang , Qu Haihong , Zhou Huaxian , Gu Shengyan , Wang Tianhua
Published: August 2019

PURPOSE:

The purpose of this study was to investigate the effect of a nurse-led multicomponent intervention on ostomy-related complications, self-efficacy, and health-related quality of life in patients with an ileal conduit.

DESIGN:

Randomized controlled trial.

SAMPLE AND SETTING:

Forty-six patients who underwent radical cystectomy and creation of an ileal conduit participated in the trial; data were collected over a 6-month period. The study setting was Shanghai Pudong Hospital, affiliated with Fudan University, located in Shanghai, China.

METHODS:

Participants were randomly allocated to an experimental or control group. Participants in the control group received routine care over a 6-month period following ostomy surgery, while those in the experimental group received a nurse-led, multicomponent, structured intervention delivered by an ostomy care team. The Chinese language versions of the Stoma Self-Efficacy Scale (SSES) and the City of Hope Quality of Life-Ostomy (COHQOL-O) questionnaire were used to assess self-efficacy in stoma care and health-related quality of life. Ostomy-related complications including peristomal moisture-associated skin damage and uric acid crystal deposits in the peristomal area were also assessed. Fisher's exact test was used to compare the incidence of ostomy-related complications between the 2 groups. Independent-samples t tests were used to compare SSES and COHQOL-O scores.

RESULTS:

No statistically significant differences were found between demographic characteristics of the control and experimental groups. After 6 months, the incidence of complications was significantly lower in the experimental group as compared to the control group (4.35% vs 30.43%, P = .047). In addition, the mean SSES score was significantly higher in the experimental group (indicating greater self-efficacy in stoma care) (107.13 ± 11.87 vs 85.65 ± 12.87, P = .000), and the mean COHQOL-O score was also significantly higher in the experimental group, indicating higher health-related quality of life (154.48 ± 16.01 vs 138.26 ± 13.42, P = .001).

CONCLUSION:

The nurse-led multicomponent intervention provided by the ostomy care team reduced ostomy-related complications and improved the self-efficacy level and health-related quality of life in persons with a new urostomy.
Resilience of lake biogeochemistry to boreal-forest wildfires during the late Holocene
Authors: Chipman Melissa L. , Hu Feng Sheng
Published: August 2019

Novel fire regimes are expected in many boreal regions, and it is unclear how biogeochemical cycles will respond. We leverage fire and vegetation records from a highly flammable ecoregion in Alaska and present new lake-sediment analyses to examine biogeochemical responses to fire over the past 5300 years. No significant difference exists in δ
13
C, %C, %N, C : N, or magnetic susceptibility between pre-fire, post-fire, and fire samples. However, δ
15
N is related to the timing relative to fire (
χ
2
= 19.73,
p
< 0.0001), with higher values for fire-decade samples (3.2 ± 0.3‰) than pre-fire (2.4 ± 0.2‰) and post-fire (2.2 ± 0.1‰) samples. Sediment δ
15
N increased gradually from 1.8 ± 0.6 to 3.2 ± 0.2‰ over the late Holocene, probably as a result of terrestrial-ecosystem development. Elevated δ
15
N in fire decades likely reflects enhanced terrestrial nitrification and/or deeper permafrost thaw depths immediately following fire. Similar δ
15
N values before and after fire decades suggest that N cycling in this lowland-boreal watershed was resilient to fire disturbance. However, this resilience may diminish as boreal ecosystems approach climate-driven thresholds of vegetation structure, permafrost thaw and fire.
Evolution of increased virulence is associated with decreased spite in the insect-pathogenic bacterium
Xenorhabdus nematophila
Authors: Bhattacharya Amrita , Toro Díaz Valeria C. , Morran Levi T. , Bashey Farrah
Published: August 2019

Disease virulence may be strongly influenced by social interactions among pathogens, both during the time course of an infection and evolutionarily. Here, we examine how spiteful bacteriocin production in the insect-pathogenic bacterium
Xenorhabdus nematophila
is evolutionarily linked to its virulence. We expected a negative correlation between virulence and spite owing to their inverse correlations with growth. We examined bacteriocin production and growth across 14 experimentally evolved lineages that show faster host-killing relative to their ancestral population. Consistent with expectations, these more virulent lineages showed reduced bacteriocin production and faster growth relative to the ancestor. Further, bacteriocin production was negatively correlated with growth across the examined lineages. These results strongly support an evolutionary trade-off between virulence and bacteriocin production and lend credence to the view that disease management can be improved by exploiting pathogen social interactions.
Oncogenic MYC amplifies mitotic perturbations
Authors: Littler Samantha , Sloss Olivia , Geary Bethany , Pierce Andrew , Whetton Anthony D. , Taylor Stephen S.
Published: August 2019

The oncogenic transcription factor MYC modulates vast arrays of genes, thereby influencing numerous biological pathways including biogenesis, metabolism, proliferation, apoptosis and pluripotency. When deregulated, MYC drives genomic instability via several mechanisms including aberrant proliferation, replication stress and ROS production. Deregulated MYC also promotes chromosome instability, but less is known about how MYC influences mitosis. Here, we show that deregulating MYC modulates multiple aspects of mitotic chromosome segregation. Cells overexpressing MYC have altered spindle morphology, take longer to align their chromosomes at metaphase and enter anaphase sooner. When challenged with a variety of anti-mitotic drugs, cells overexpressing MYC display more anomalies, the net effect of which is increased micronuclei, a hallmark of chromosome instability. Proteomic analysis showed that MYC modulates multiple networks predicted to influence mitosis, with the mitotic kinase PLK1 identified as a central hub. In turn, we show that MYC modulates several PLK1-dependent processes, namely mitotic entry, spindle assembly and SAC satisfaction. These observations thus underpin the pervasive nature of oncogenic MYC and provide a mechanistic rationale for MYC's ability to drive chromosome instability.
Multilevel selection as Bayesian inference, major transitions in individuality as structure learning
Authors: Czégel Dániel , Zachar István , Szathmáry Eörs
Published: August 2019

Complexity of life forms on the Earth has increased tremendously, primarily driven by subsequent evolutionary transitions in individuality, a mechanism in which units formerly being capable of independent replication combine to form higher-level evolutionary units. Although this process has been likened to the recursive combination of pre-adapted sub-solutions in the framework of learning theory, no general mathematical formalization of this analogy has been provided yet. Here we show, building on former results connecting replicator dynamics and Bayesian update, that (i) evolution of a hierarchical population under multilevel selection is equivalent to Bayesian inference in hierarchical Bayesian models and (ii) evolutionary transitions in individuality, driven by synergistic fitness interactions, is equivalent to learning the structure of hierarchical models via Bayesian model comparison. These correspondences support a learning theory-oriented narrative of evolutionary complexification: the complexity and depth of the hierarchical structure of individuality mirror the amount and complexity of data that have been integrated about the environment through the course of evolutionary history.
Sex-linked genetic diversity originates from persistent sociocultural processes at microgeographic scales
Authors: Chung Ning Ning , Jacobs Guy S. , Sudoyo Herawati , Malik Safarina G. , Chew Lock Yue , Lansing J. Stephen , Cox Murray P.
Published: August 2019

Population genetics has been successful at identifying the relationships between human groups and their interconnected histories. However, the link between genetic demography inferred at large scales and the individual human behaviours that ultimately generate that demography is not always clear. While anthropological and historical context are routinely presented as adjuncts in population genetic studies to help describe the past, determining how underlying patterns of human sociocultural behaviour impact genetics still remains challenging. Here, we analyse patterns of genetic variation in village-scale samples from two islands in eastern Indonesia, patrilocal Sumba and a matrilocal region of Timor. Adopting a ‘process modelling’ approach, we iteratively explore combinations of structurally different models as a thinking tool. We find interconnected socio-genetic interactions involving sex-biased migration, lineage-focused founder effects, and on Sumba, heritable social dominance. Strikingly, founder ideology, a cultural model derived from anthropological and archaeological studies at larger regional scales, has both its origins and impact at the scale of villages. Process modelling lets us explore these complex interactions, first by circumventing the complexity of formal inference when studying large datasets with many interacting parts, and then by explicitly testing complex anthropological hypotheses about sociocultural behaviour from a more familiar population genetic standpoint.
Indirect interactions influence contact network structure and diffusion dynamics
Authors: Shahzamal Md , Jurdak Raja , Mans Bernard , de Hoog Frank
Published: August 2019

Interaction patterns at the individual level influence the behaviour of diffusion over contact networks. Most of the current diffusion models only consider direct interactions, capable of transferring infectious items among individuals, to build transmission networks of diffusion. However, delayed indirect interactions, where a susceptible individual interacts with infectious items after the infected individual has left the interaction space, can also cause transmission events. We define a diffusion model called the same place different time transmission (SPDT)-based diffusion that considers transmission links for these indirect interactions. Our SPDT model changes the network dynamics where the connectivity among individuals varies with the decay rates of link infectivity. We investigate SPDT diffusion behaviours by simulating airborne disease spreading on data-driven contact networks. The SPDT model significantly increases diffusion dynamics with a high rate of disease transmission. By making the underlying connectivity denser and stronger due to the inclusion of indirect transmissions, SPDT models are more realistic than same place same time transmission (SPST)-based models for the study of various airborne disease outbreaks. Importantly, we also find that the diffusion dynamics including indirect links are not reproducible by the current SPST models based on direct links, even if both SPDT and SPST networks assume the same underlying connectivity. This is because the transmission dynamics of indirect links are different from those of direct links. These outcomes highlight the importance of the indirect links for predicting outbreaks of airborne diseases.
Dyakonov–Voigt surface waves
Authors: Mackay Tom G. , Zhou Chenzhang , Lakhtakia Akhlesh
Published: August 2019

Electromagnetic surface waves guided by the planar interface of an isotropic dielectric medium and a uniaxial dielectric medium, both non-dissipative, were considered, the optic axis of the uniaxial medium lying in the interface plane. Whereas this interface is known to support the propagation of Dyakonov surface waves when certain constraints are satisfied by the constitutive parameters of the two partnering mediums, we identified a different set of constraints that allow the propagation of surface waves of a new type. The fields of the new surface waves, named Dyakonov–Voigt (DV) surface waves, decay as the product of a linear and an exponential function of the distance from the interface in the anisotropic medium, whereas the fields of the Dyakonov surface waves decay only exponentially in the anisotropic medium. In contrast to Dyakonov surface waves, the wavenumber of a DV surface wave can be found analytically. Also, unlike Dyakonov surface waves, DV surface waves propagate only in one direction in each quadrant of the interface plane.
Land sparing to make space for species dependent on natural habitats and high nature value farmland
Authors: Feniuk Claire , Balmford Andrew , Green Rhys E.
Published: August 2019

Empirical evidence from four continents indicates that human food demand may be best reconciled with biodiversity conservation through sparing natural habitats by boosting agricultural yields. This runs counter to the conservation paradigm of wildlife-friendly farming, which is influential in Europe, where many species are dependent on low-yielding high nature value farmland threatened by both intensification and abandonment. In the first multi-taxon population-level test of land-sparing theory in Europe, we quantified how population densities of 175 bird and sedge species varied with farm yield across 26 squares (each with an area of 1 km
2
) in eastern Poland. We discovered that, as in previous studies elsewhere, simple land sparing, with only natural habitats on spared land, markedly out-performed land sharing in its effect on region-wide projected population sizes. However, a novel ‘three-compartment’ land-sparing approach, in which about one-third of spared land is assigned to very low-yield agriculture and the remainder to natural habitats, resulted in least-reduced projected future populations for more species. Implementing the three-compartment model would require significant reorganization of current subsidy regimes, but would mean high-yield farming could release sufficient land for species dependent on both natural and high nature value farmland to persist.
Descriptive epidemiology of physical activity energy expenditure in UK adults. The Fenland Study
Authors: Lindsay Tim , Westgate Kate , Wijndaele Katrien , Hollidge Stefanie , Kerrison Nicola , Forouhi Nita , Griffin Simon , Wareham Nick , Brage Søren
Published: August 2019

Background

Physical activity (PA) plays a role in the prevention of a range of diseases including obesity and cardiometabolic disorders. Large population-based descriptive studies of PA, incorporating precise measurement, are needed to understand the relative burden of insufficient PA levels and to inform the tailoring of interventions. Combined heart and movement sensing enables the study of physical activity energy expenditure (PAEE) and intensity distribution. We aimed to describe the sociodemographic correlates of PAEE and moderate-to-vigorous physical activity (MVPA) in UK adults.

Methods

The Fenland study is a population-based cohort study of 12,435 adults aged 29–64 years-old in Cambridgeshire, UK. Following individual calibration (treadmill), participants wore a combined heart rate and movement sensor continuously for 6 days in free-living, from which we derived PAEE (kJ•day-1•kg-1) and time in MVPA (>3 & >4 METs) in bouts greater than 1 minute and 10 minutes. Socio-demographic information was self-reported. Stratum-specific summary statistics and multivariable analyses were performed.

Results

Women accumulated a mean(sd) 50(20) kJ•day-1•kg-1 of PAEE, and 83(67) and 33(39) minutes•day-1 of 1-min bouted and 10-min bouted MVPA respectively. By contrast, men recorded 59(23) kJ•day-1•kg-1, 124(84) and 60(58) minutes•day-1. Age and BMI were also important correlates of PA. Association with age was inverse in both sexes, more strongly so for PAEE than MVPA. Obese individuals accumulated less PA than their normal-weight counterparts whether considering PAEE or allometrically-scaled PAEE (-10 kJ•day-1•kg-1 vs -15 kJ•day-1•kg-2/3 in men). Higher income and manual work were associated with higher PA; manual workers recorded 13-16 kJ•kg-1•day-1 more PAEE than sedentary counterparts. Overall, 86% of women and 96% of men accumulated 21.4 min•day-1 of MVPA (>3 METs) on average (150 minutes per week). These values were 49% and 74% if only considering bouts >10 min (15% and 31% for >4 METs).

Conclusions

PA varied by age, sex and BMI, and was higher in manual workers and those with higher incomes. Light physical activity was the main driver of PAEE; a component of PA that is currently not quantified as a target in UK guidelines.
Acute and Chronic Molecular Signatures and Associated Symptoms of Blast Exposure in Military Breachers
Authors: Wang Zhaoyu , Wilson Caroline M , Mendelev Natalia , Ge Yongchao , Galfalvy Hanga , Elder Gregory , Ahlers Stephen , Yarnell Angela M , LoPresti Matthew L , Kamimori Gary , Carr Walter , Haghighi Fatemeh
Published: August 2019

Injuries from exposure to explosions rose dramatically during the Iraq and Afghanistan wars, which motivated investigations of blast-related neurotrauma and operational breaching. In this study, military “breachers” were exposed to controlled, low-level blast during a 10-day explosive breaching course. Using an omics approach, we assessed epigenetic, transcriptional, and inflammatory profile changes in blood from operational breaching trainees, with varying levels of lifetime blast exposure, along with daily self-reported symptoms (with tinnitus, headaches, and sleep disturbances as the most frequently reported). Although acute exposure to blast did not confer epigenetic changes, specifically in DNA methylation, differentially methylated regions (DMRs) with coordinated gene expression changes associated with chronic lifetime cumulative blast exposures were identified. The accumulative effect of blast showed increased methylation of PAX8 antisense transcript with coordinated repression of gene expression, which has been associated with sleep disturbance. DNA methylation analyses conducted in conjunction with reported symptoms of tinnitus in the low vs. high blast incidents groups identified DMRS in KCNE1 and CYP2E1 genes. KCNE1 and CYP2E1 showed the expected inverse correlation between DNA methylation and gene expression, which have been previously implicated in noise related hearing loss. Although no significant transcriptional changes were observed in samples obtained at the onset of the training course relative to chronic cumulative blast, we identified a large number of transcriptional perturbations acutely pre- versus post-blast exposure. Acutely, 67 robustly differentially expressed genes (fold change ≥1.5), including UFC1 and YOD1, ubiquitin-related proteins were identified. Inflammatory analyses of cytokines and chemokines revealed dysregulation of MCP-1, GCSF, HGF, MCSF, and RANTES acutely following blast exposure. These data show the importance of an omics approach, revealing that transcriptional and inflammatory biomarkers capture acute low-level blast overpressure exposure, whereas DNA methylation marks encapsulate chronic long-term symptoms.
IFN-independent G0 arrest and SAMHD1 activation following TLR4 activation in macrophages
Authors: Mlcochova P. , Winstone H. , Zuliani-Alvarez L. , Gupta R.K.
Published: August 2019

Monocyte-derived macrophages mostly reside in a resting, G0 state, expressing high levels of dephosphorylated, active SAMHD1. We have previously shown that macrophages can re-enter the cell cycle without division, into a G1-like state. This cell cycle re-entry is accompanied by phosphorylation of the dNTP hydrolase/ antiviral restriction factor SAMHD1 at T592 by the cyclin-dependent kinase CDK1. HIV-1 successfully infects macrophages in G1 through exploiting this naturally occurring window of opportunity where SAMHD1 antiviral activity is de-activated.

Here we demonstrate for the first time that LPS activation of the pathogen associated molecular pattern (PAMP) receptor TLR4 induces G0 arrest in human macrophages. We show this G0 arrest is MyD88-independent and therefore NFkB independent. Furthermore, the effect of TLR4 activation on cell cycle is regulated by (a) the canonical IFN-dependent pathway following TBK1 activation and IRF3 translocation and (b) an IFN-independent pathway that occurs prior to TBK1 activation, and that is accompanied by CDK1 downregulation, p21 upregulation and SAMHD1 dephosphorylation at T592. Furthermore, we show by siRNA knockdown of SAMHD1 that the interferon independent pathway activated by TLR4 is able to potently block HIV-1 infection in macrophages specifically via SAMHD1. Finally, ingestion of whole E. Coli and TLR4 activation by macrophages also activates SAMHD1 via the interferon independent pathway.

Together, these data demonstrate that macrophages can rapidly activate an intrinsic cell arrest and anti-viral state by activation of TLR4 prior to IFN secretion, thereby highlighting the importance of cell cycle regulation as a response to danger signals in human macrophages. Interferon independent activation of SAMHD1 by TLR4 represents a novel mechanism for limiting the HIV-1 reservoir size and should be considered for host-directed therapeutic approaches that may contribute to curative interventions.
Draft genome sequences of five Proteobacteria isolated from Lechuguilla Cave, New Mexico, USA: Insights into taxonomy and quorum-sensing
Authors: Gan Han Ming , Wengert Peter C. , Barton Hazel A. , Hudson André O. , Savka Michael A.
Published: August 2019

Genomic resources remain scarce for bacteria isolated from oligotrophic caves. We sequenced the genomes of five Proteobacteria isolated from Lechuguilla Cave in New Mexico, USA. Genome-based phylogeny indicates that each strain belongs to a distinct genus. Two Rhizobiaceae isolates possess the genomic potential for the biosynthesis of acyl-homoserine lactone.
SILAC-based quantitative proteomics reveals pleiotropic, phenotypic modulation in primary murine macrophages infected with the protozoan pathogenLeishmania donovani
Authors: Smirlis Despina , Dingli Florent , Pescher Pascale , Prina Eric , Loew Damarys , Rachidi Najma , Späth Gerald F.
Published: August 2019

Leishmaniases are major vector-borne tropical diseases responsible for great human morbidity and mortality, caused by protozoan, trypanosomatid parasites of the genusLeishmania.In the mammalian host parasites survive and multiply within mononuclear phagocytes, especially macrophages. However, the underlying mechanisms by whichLeishmaniaspp affect their host, are not fully understood. Herein, proteomic alterations of primary bone marrow-derived, BALB/c macrophages are documented after 72 h of infection withLeishmania donovaniinsect-stage promastigotes, with the use of a SILAC-based, quantitative proteomics approach. The protocol was optimised by combining strong anion exchange and gel electrophoresis fractionation that displayed similar depth of analysis (>5500 proteins). Our analyses revealed 86 differentially modulated proteins (35 showing increased and 51 decreased abundance) in response toLeishmania donovaniinfection. The proteomics results were validated by analysing the abundance of selected proteins. IntracellularLeishmania donovaniinfection led to changes in various host cell biological processes, including primary metabolism and catabolic process, with a significant enrichment in lysosomal organisation. Overall, our analysis allows new technical insight into the challenges of quantitative proteomics applied on primary cells, and establishes the first proteome ofbona fideprimary macrophages infectedex vivowithLeishmania donovani, revealing new mechanisms acting at the host/pathogen interface.
Loss of MLKL Decreases Necrotic Core but Increases Macrophage Lipid Accumulation In Atherosclerosis
Authors: Rasheed Adil , Robichaud Sabrina , Nguyen My-Anh , Geoffrion Michele , Cottee Mary Lynn , Dennison Taylor , Pietrangelo Antonietta , Lee Richard , Ouimet Mireille , Rayner Katey J
Published: August 2019

Objectives

During the advancement of atherosclerosis, the cellularity of the plaque is governed by the influx of monocyte-derived macrophages and their turnover via apoptotic and non-apoptotic forms of cell death. Previous reports have demonstrated that programmed necrosis, or necroptosis, of macrophages within the plaque contribute to necrotic core formation. Knockdown or inhibition of the necrosome components RIPK1 and RIPK3 slow the progression of atherosclerosis, and activation of the terminal step of necroptosis, MLKL, has been demonstrated in advanced human atherosclerotic plaques. However, whether MLKL directly contributes to lesion development and necrotic core formation has not been investigated.

Approaches and Results

MLKL expression was knocked down in atherogenic Apoe- knockout mice via subcutaneous administration of antisense oligonucleotides (ASO). During advanced atherogenesis, Mlkl knockdown potently reduced cell death in the plaque, with a significant reduction in the necrotic core. However, total lesion area in the aortic sinus remained unchanged. Furthermore, treatment with the MLKL ASO unexpectedly reduced circulating cholesterol levels compared to control ASO, while staining for lipids within the plaque was significantly increased. Peritoneal macrophages transfected with the MLKL ASO showed increased lipid loading upon incubation with modified cholesterol-rich lipoproteins. In lipid-loaded macrophages, MLKL co-localized with Rab7, a marker of the late endosome.

Conclusions

These studies confirm the requirement for MLKL as the executioner of necroptosis, and as such a significant contributor to the necrotic core during atherogenesis. We also identified a previously unknown role for MLKL in interacting with endosomal trafficking components to regulate lipid uptake in macrophages during atherogenesis.
Physical basis of lumen shape and stability in a simple epithelium
Authors: Vasquez Claudia G. , Vachharajani Vipul T. , Garzon-Coral Carlos , Dunn Alexander R.
Published: August 2019

A continuous sheet of epithelial cells surrounding a hollow opening, or lumen, defines the basic topology of numerous organs.De novolumen formation is a central feature of embryonic development whose dysregulation leads to congenital and acquired diseases of the kidney and other organs. Hydrostatic pressure has been proposed to drive lumen expansion, a view that is supported by recent experiments in the mouse blastocyst. High luminal pressure should produce lumen surfaces that bow outwards toward the surrounding cells. However, lumens formed in other embryonic tissues adopt highly irregular shapes, with cell apical faces that are bowed inward, suggesting that pressure may not be the dominant contributor to lumen growth in all cases. We used three-dimensional live-cell imaging to study the physical mechanism of lumen formation in Madin Darby Canine Kidney (MDCK) cell spheroids, a canonical cell-culture model for lumenogenesis. Our experiments revealed that neither lumen pressure nor the actomyosin cytoskeleton were required to maintain lumen shape or stability. Instead, we find that, in our model system, lumen shape results from simple geometrical factors tied to the establishment of apico-basal polarity. A quantitative physical model that incorporates cell geometry, cortical tension, and intraluminal pressure can account for our observations as well as cases in which pressure indeed plays a dominant role. Our results thus support a unifying physical mechanism for the formation of luminal openings in a variety of physiological contexts.
The effects of direct brain stimulation in humans depend on frequency, amplitude, and white-matter proximity
Authors: Mohan Uma R. , Watrous Andrew J. , Miller Jonathan F. , Lega Bradley C. , Sperling Michael R. , Worrell Gregory A. , Gross Robert E. , Zaghloul Kareem A. , Jobst Barbara C. , Davis Kathryn A. , Sheth Sameer A. , Stein Joel M. , Das Sandhitsu R. , Gorniak Richard , Wanda Paul A. , Rizzuto Daniel S. , Kahana Michael J. , Jacobs Joshua
Published: August 2019

Researchers have used direct electrical brain stimulation to treat a range of neurological and psychiatric disorders. However, for brain stimulation to be maximally effective, clinicians and researchers should optimize stimulation parameters according to desired outcomes. To examine how different kinds of stimulation affect human brain activity, we compared the changes in neuronal activity that resulted from stimulation at a range of frequencies, amplitudes, and locations with direct human brain recordings. We recorded human brain activity directly with electrodes that were implanted in widespread regions across 106 neurosurgical epilepsy patients while systematically stimulating across a range of parameters and locations. Overall, stimulation most often had an inhibitory effect on neuronal activity, consistent with earlier work. When stimulation excited neuronal activity, it most often occurred from high-frequency stimulation. These effects were modulated by the location of the stimulating electrode, with stimulation sites near white matter more likely to cause excitation and sites near gray matter more likely to inhibit neuronal activity. By characterizing how different stimulation parameters produced specific neuronal activity patterns on a large scale, our results help guide clinicians and researchers when designing stimulation protocols to cause precisely targeted changes in human brain activity.
A comprehensive analysis of racial disparities in chemical biomarker concentrations in United States women, 1999-2014
Authors: Nguyen Vy Kim , Kahana Adam , Heidt Julien , Polemi Katelyn , Kvasnicka Jacob , Jolliet Olivier J. , Colacino Justin A.
Published: August 2019

Background

Stark racial disparities in disease incidence among American women remains a persistent public health challenge. These disparities likely result from complex interactions between genetic, social, lifestyle, and environmental risk factors. The influence of environmental risk factors, such as chemical exposure, however, may be substantial and is poorly understood.

Objectives

We quantitatively evaluated chemical-exposure disparities by race/ethnicity and age in United States (US) women by using biomarker data for 143 chemicals from the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

Methods

We applied a series of survey-weighted, generalized linear models using data from the entire NHANES women population and age-group stratified subpopulations. The outcome was chemical biomarker concentration and the main predictor was race/ethnicity with adjustment for age, socioeconomic status, smoking habits, and NHANES cycle.

Results

The highest disparities across non-Hispanic Black, Mexican American, Other Hispanic, and other race/multiracial women were observed for pesticides and their metabolites, including 2,5-dichlorophenol, o,p’-DDE, beta-hexachlorocyclohexane, and 2,4-dichlorophenol, along with personal care and consumer product compounds. The latter included parabens, monoethyl phthalate, and several metals, such as mercury and arsenic. Moreover, for Mexican American, Other Hispanic, and non-Hispanic black women, there were several exposure disparities that persisted across age groups, such as higher 2,4- and 2,5-dichlorophenol concentrations. Exposure differences for methyl and propyl parabens, however, were the starkest between non-Hispanic black and non-Hispanic white children with average differences exceeding 4 folds.

Discussions

We systematically evaluated differences in chemical exposures across women of various race/ethnic groups and across age groups. Our findings could help inform chemical prioritization in designing epidemiological and toxicological studies. In addition, they could help guide public health interventions to reduce environmental and health disparities across populations.