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Monoamine oxidase (MAO) metabolizes cytosolic dopamine (DA), thereby limiting auto-oxidation, but is also thought to generate cytosolic hydrogen peroxide (H2O2). We show that MAO metabolism of DA does not increase cytosolic H2O2 but leads to mitochondrial electron transport chain (ETC) activity. This is dependent upon MAO anchoring to the outer mitochondrial membrane and shuttling electrons through the intermembrane space to support the bioenergetic demands of phasic DA release.

Rapid and significant range expansion of both the Zika virus (ZIKV) and its Aedes vector species has resulted in the declaration of ZIKV as a global health threat. Successful transmission of ZIKV by its vector requires a complex series of interactions between these entities including the establishment, replication and dissemination of the virus within the mosquito. The metabolic conditions within the mosquito tissues play a critical role in mediating the crucial processes of viral infection and replication and represent targets for prevention of virus transmission. In this study, we carried out a comprehensive metabolomic phenotyping of ZIKV infected and uninfected Ae. albopictus by untargeted analysis of primary metabolites, lipids and biogenic amines. We performed a comparative metabolomic study of infection state with the aim of understanding the biochemical changes resulting from the interaction between the ZIKV and its vector. We have demonstrated that ZIKV infection results in changes to the cellular metabolic environment including a significant enrichment of inosine and pseudo-uridine (Ψ) levels which may be associated with RNA editing activity. In addition, infected mosquitoes demonstrate a hypoglycemic phenotype and show significant increases in the abundance of metabolites such as prostaglandin H2, leukotriene D4 and protoporphyrinogen IX which are associated with antiviral activity. These provide a basis for understanding the biochemical response to ZIKV infection and pathology in the vector. Future mechanistic studies targeting these ZIKV infection responsive metabolites and their associated biosynthetic pathways can provide inroads to identification of mosquito antiviral responses with infection blocking potential.

[This corrects the article DOI: 10.3389/fmicb.2020.559035.].

Abstract Background This review aimed to identify variables influencing clinicians’ application of spinal manipulative therapy (SMT) for persistent spine pain after lumbar surgery (PSPS-2). We hypothesized markers of reduced clinical/surgical complexity would be associated with greater odds of applying SMT to the lumbar region, use of manual-thrust lumbar SMT, and SMT within 1-year post-surgery as primary outcomes; and chiropractors would have increased odds of using lumbar manual-thrust-SMT compared to other practitioners. Methods Per our published protocol, observational studies describing adults receiving SMT for PSPS-2 were included. PubMed, Web of Science, Scopus, OVID, PEDro, and Index to Chiropractic Literature were searched from inception to January 6, 2022. Individual patient data (IPD) were requested from contact authors when needed for selection criteria. Data extraction and a customized risk-of-bias rubric were completed in duplicate. Odds ratios (ORs) for primary outcomes were calculated using binary logistic regressions, with covariates including age, sex, symptom distribution, provider, motion segments, spinal implant, and surgery-to-SMT interval. Results 71 articles were included describing 103 patients (mean age 52 ± 15, 55% male). The most common surgeries were laminectomy (40%), fusion (34%), and discectomy (29%). Lumbar SMT was used in 85% of patients; and of these patients was non-manual-thrust in 59%, manual-thrust in 33%, and unclear in 8%. Clinicians were most often chiropractors (68%). SMT was used > 1-year post-surgery in 66% of cases. While no primary outcomes reached significance, non-reduced motion segments approached significance for predicting use of lumbar-manual-thrust SMT (OR 9.07 [0.97–84.64], P = 0.053). Chiropractors were significantly more likely to use lumbar-manual-thrust SMT (OR 32.26 [3.17–327.98], P = 0.003). A sensitivity analysis omitting high risk-of-bias cases (missing ≥ 25% IPD) revealed similar results. Conclusions Clinicians using SMT for PSPS-2 most often apply non-manual-thrust SMT to the lumbar spine, while chiropractors are more likely to use lumbar-manual-thrust SMT relative to other providers. As non-manual-thrust SMT may be gentler, the proclivity towards this technique suggests providers are cautious when applying SMT after lumbar surgery. Unmeasured variables such as patient or clinician preferences, or limited sample size may have influenced our findings. Large observational studies and/or international surveys are needed for an improved understanding of SMT use for PSPS-2. Systematic review registration PROSPERO (CRD42021250039).

Abstract Background Individuals who use a language other than English for medical care are at risk for disparities related to healthcare safety, patient-centered care, and quality. Professional interpreter use decreases these disparities but remains underutilized, despite widespread access and legal mandates. In this study, we compare two discrete implementation strategies for improving interpreter use: (1) enhanced education targeting intrapersonal barriers to use delivered in a scalable format (interactive web-based educational modules) and (2) a strategy targeting system barriers to use in which mobile video interpreting is enabled on providers’ own mobile devices. Methods We will conduct a type 3 hybrid implementation-effectiveness study in 3–5 primary care organizations, using a sequential multiple assignment randomized trial (SMART) design. Our primary implementation outcome is interpreter use, calculated by matching clinic visits to interpreter invoices. Our secondary effectiveness outcome is patient comprehension, determined by comparing patient-reported to provider-documented visit diagnosis. Enrolled providers (n = 55) will be randomized to mobile video interpreting or educational modules, plus standard interpreter access. After 9 months, providers with high interpreter use will continue as assigned; those with lower use will be randomized to continue as before or add the alternative strategy. After another 9 months, both strategies will be available to enrolled providers for 9 more months. Providers will complete 2 surveys (beginning and end) and 3 in-depth interviews (beginning, middle, and end) to understand barriers to interpreter use, based on the Theoretical Domains Framework. Patients who use a language other than English will be surveyed (n = 648) and interviewed (n = 75) following visits with enrolled providers to understand their experiences with communication. Visits will be video recorded (n = 100) to assess fidelity to assigned strategies. We will explore strategy mechanism activation to refine causal pathway models using a quantitative plus qualitative approach. We will also determine the incremental cost-effectiveness of each implementation strategy from a healthcare organization perspective, using administrative and provider survey data. Discussion Determining how these two scalable strategies, alone and in sequence, perform for improving interpreter use, the mechanisms by which they do so, and at what cost, will provide critical insights for addressing a persistent cause of healthcare disparities. Trial registration NCT05591586.

The study of a well-preserved collection of discodorid nudibranchs collected in Koumac, New Caledonia, revealed the presence of seven species new to science belonging to the genera Atagema, Jorunna, Rostanga, and Sclerodoris, although some of the generic assignments are tentative as the phylogeny of Discodorididae remains unresolved. Moreover, a poorly known species of Atagema originally described from New Caledonia is re-described and the presence of Sclerodoris tuberculata in New Caledonia is confirmed with molecular data. All the species described herein are highly cryptic on their food source and in the context of the present study the term “cryptic” is used to denote such species. This paper highlights the importance of comprehensive collecting efforts to identify and document well-camouflaged taxa.

Abstract Stone-tool making is an ancient human skill thought to have played a key role in the bio-cultural co-evolutionary feedback that produced modern brains, culture, and cognition. To test the proposed evolutionary mechanisms underpinning this hypothesis we studied stone-tool making skill learning in modern participants and examined interactions between individual neurostructural differences, plastic accommodation, and culturally transmitted behavior. We found that prior experience with other culturally transmitted craft skills increased both initial stone tool-making performance and subsequent neuroplastic training effects in a frontoparietal white matter pathway associated with action control. These effects were mediated by the effect of experience on pre-training variation in a frontotemporal pathway supporting action semantic representation. Our results show that the acquisition of one technical skill can produce structural brain changes conducive to the discovery and acquisition of additional skills, providing empirical evidence for bio-cultural feedback loops long hypothesized to link learning and adaptive change.

Experiences gained through in person (in-situ) interactions with ecosystems provide cultural ecosystem services. These services are difficult to assess because they are non-material, vary spatially and have strong perceptual characteristics. Data obtained from social media can provide spatially-explicit information regarding some in-situ cultural ecosystem services by serving as a proxy for visitation. These data can identify environmental characteristics (natural, human and built capital) correlated with visitation and, therefore, the types of places used for in-situ environmental interactions. A range of spatial models can be applied in this way that vary in complexity and can provide information for ecosystem service assessments. We deployed four models (global regression, local regression, maximum entropy and the InVEST recreation model) to the same case-study area, County Galway, Ireland, to compare spatial models. A total of 6,752 photo-user-days (PUD) (a visitation metric) were obtained from Flickr. Data describing natural, human and built capital were collected from national databases. Results showed a blend of capital types correlated with PUD suggesting that local context, including biophysical traits and accessibility, are relevant for in-situ cultural ecosystem service flows. Average trends included distance to the coast and elevation as negatively correlated with PUD, while the presence of major roads and recreational sites, population density and habitat diversity were positively correlated. Evidence of local relationships, especially town distance, were detected using geographic weighted regression. Predicted hotspots for visitation included urban areas in the east of the region and rural, coastal areas with major roads in the west. We conclude by presenting a guide for researchers and practitioners developing cultural ecosystem service spatial models using data from social media that considers data coverage, landscape heterogeneity, computational resources, statistical expertise and environmental context.

Objectives: We aimed to 1) assess body composition using a portable technology, bioelectrical impedance analysis, (BIA) and 2) examine the associations between body composition and the discrepancy of fear of falling (FOF) and balance performance. Methods: A cross-sectional study included 121 older adults 60 years and older, 78% were female, 41% lived alone, and 71% had no history of falls. The discrepancy between fear of falling and balance performance was categorized into four groups. We found 47% rational (low FOF and normal balance), 19% incongruent (low FOF despite poor balance), 18% irrational (high FOF despite normal balance), and 16% congruent (high FOF and poor balance). Results: Body Fat Mass (BFM), Percent Body Fat (PBF), and Body Mass Index (BMI) were correlated with fear of falling and balance performance. BMI was significantly different in the rational group (p = 0.004) and incongruent group (p = 0.02) compared to the congruent group. PBF was significantly different between the incongruent (p = 0.002), irrational (p = 0.014), and rational (p

Adults (N = 54, 80.78 ± 6.08 years) who reported falling during the previous 12 months participated in a 12-week wobble board training program with internal focus or external focus (EF) instructions. Verbal manipulation checks were performed after training sessions as a self-report of the attentional foci used. The percentage of sessions in which participants reported using an EF (EF[subscript SR]) was subsequently calculated. Mean velocity and mean power frequency in the anterior-posterior (MVELO[subscript AP] and MPF[subscript AP]) and medial-lateral (MVELO[subscript ML] and MPF[subscript ML]) direction were assessed during a 35-s wobble board task at Weeks 0, 6, 12, 13, 16, and 20, with the latter three as retention tests. Piecewise linear growth models estimated treatment effects on individual growth trajectories of MVELO[subscript AP] and [subscript ML] and MPF[subscript AP] and [subscript ML] during intervention and retention periods. Regardless of condition, MVELOML significantly decreased ([pi] = -0.0019, p = 0.005) and MPF[subscript ML] increased ([pi] = 0.025, p < 0.02) during the intervention period. In analyses including interaction terms, participants in the EF group who reported greater EF[subscript SR] had superior progression of MPF[subscript AP] during the intervention ([pi] = 0.0013, p = 0.025). Verbal manipulation checks suggest a preference for and advantage of EF for facilitating postural control performance and automaticity.

Some work demonstrates toddlers show preferences in targets of their prosocial behavior, and a number of theorists have argued that young children become increasingly likely to direct their prosocial behavior to ingroup over outgroup targets with development. The goal of this study was to examine whether toddlers' early helping, sharing, and empathic distress were influenced by the race of the target person. Ninety-four White European American 18-month-old (17-19 months, M = 18.25, SD = 0.43; 55.1% male) and 24-month-old (23-25 months; M = 23.67, SD = 0.57; 53.1% male) toddlers took part in a series of tasks designed to assess children's instrumental helping, sharing, and empathic distress. These toddlers came from well-educated families (86.4% of mothers had a college degree and 73.8% of their partners had a college degree or more). In the study, the race of the needy target was manipulated, so that half of the children had the opportunity to respond prosocially to a White target and half had the opportunity to be prosocial to a Black target. The race of the needy experimenter influenced children's instrumental helping and emotional arousal in a feigned injury task, but did not influence their sharing behavior. Contrary to our hypothesis, though, the older toddlers expressed more empathic distress and arousal to the Black experimenter's feigned injury than to a White experimenter's feigned injury. Implications for theory and research aimed at understanding discriminatory prosocial behaviors between young children are discussed.

Purpose Previous studies have suggested that beta-alanine supplementation may benefit exercise performance, but current evidence regarding its effects on body composition remains unclear. This systematic review and meta-analysis aimed to investigate the effects of beta-alanine supplementation on body composition indices. Methods Online databases, including PubMed/Medline, Scopus, Web of Science, and Embase, were searched up to April 2021 to retrieve randomized controlled trials (RCTs), which examined the effect of beta-alanine supplementation on body composition indices. Meta-analyses were carried out using a random-effects model. The I2 index was used to assess the heterogeneity of RCTs. Results Among the initial 1413 studies that were identified from electronic databases search, 20 studies involving 492 participants were eligible. Pooled effect size from 20 studies indicated that beta-alanine supplementation has no effect on body mass (WMD: −0.15 kg; 95% CI: −0.78 to 0.47; p = 0.631, I2 = 0.0%, p = 0.998), fat mass (FM) (WMD: −0.24 kg; 95% CI: −1.16 to 0.68; p = 0.612, I2 = 0.0%, p = 0.969), body fat percentage (BFP) (WMD: −0.06%; 95% CI: −0.53 to 0.40; p = 0.782, I2 = 0.0%, p = 0.936), and fat-free mass (FFM) (WMD: 0.05 kg; 95% CI: −0.71 to 0.82; p = 0.889, I2 = 0.0%, p = 0.912). Subgroup analyses based on exercise type (resistance training [RT], endurance training [ET], and combined training [CT]), study duration (

This position stand aims to provide an evidence-based summary of the energy and nutritional demands of tactical athletes to promote optimal health and performance while keeping in mind the unique challenges faced due to work schedules, job demands, and austere environments. After a critical analysis of the literature, the following nutritional guidelines represent the position of the International Society of Sports Nutrition (ISSN). General Recommendations Nutritional considerations should include the provision and timing of adequate calories, macronutrients, and fluid to meet daily needs as well as strategic nutritional supplementation to improve physical, cognitive, and occupational performance outcomes; reduce risk of injury, obesity, and cardiometabolic disease; reduce the potential for a fatal mistake; and promote occupational readiness. Military Recommendations Energy demands should be met by utilizing the Military Dietary Reference Intakes (MDRIs) established and codified in Army Regulation 40-25. Although research is somewhat limited, military personnel may also benefit from caffeine, creatine monohydrate, essential amino acids, protein, omega-3-fatty acids, beta-alanine, and L-tyrosine supplementation, especially during high-stress conditions. First Responder Recommendations Specific energy needs are unknown and may vary depending on occupation-specific tasks. It is likely the general caloric intake and macronutrient guidelines for recreational athletes or the Acceptable Macronutrient Distribution Ranges for the general healthy adult population may benefit first responders. Strategies such as implementing wellness policies, setting up supportive food environments, encouraging healthier food systems, and using community resources to offer evidence-based nutrition classes are inexpensive and potentially meaningful ways to improve physical activity and diet habits. The following provides a more detailed overview of the literature and recommendations for these populations.

Background The demands of typical daily activities require a constant level of alertness and attention. Multi-ingredient, caffeine-containing supplements have been shown to improve measures of cognitive performance. As many of these supplements become readily available, efficacy of each should be evaluated. Therefore, the purpose of this study is to examine the effects of the 4D dietary supplement on cognition, reaction time, and reactive agility. Methods Seventeen healthy males (n = 8) and females (n = 9) between the ages of 18–40 years old (22.8 ± 2.9 years; 167.3 ± 9.6 cm; 65.4 ± 10.9 kg) participated in this double-blind, randomized crossover study. Participants completed three baseline reaction time assessments on the Dynavision and one baseline multiple object tracking assessment on the Neurotracker. Participants then consumed the oral multi-ingredient supplement containing 150 mg of caffeine or non-caffeinated placebo, mixed with 24 ounces of water, and rested for 45 minutes. Following the rest period, participants completed an additional three reaction time assessments and one multiple object tracking (MOT) assessment, as well as 6–12 trials of the Y-reactive agility test. Repeated measures ANOVAs were used to evaluate YRA performance and change values for Dynavision RT, Dynavision score, and MOT speed with either 4D dietary supplement or placebo. Results A significant time × supplement interaction was shown for MOT speed (p = .040, d = .543). Change scores in MOT speed were significantly different from zero following 4D (mean: 0.224 au; 95% confidence interval: 0.050 to 0.398 au) but not placebo supplementation (mean: −0.046 au; 95% confidence interval: −0.220 to 0.127 au). No time × supplement interaction was shown for Dynavision RT (p = .056, d = −.499) or Dynavision score (p = .093, d = .434). No differences were shown for YRA scores following supplementation for the right side (p = .241, d = −.295) or left side (p = .378, d = −.220). Conclusion The 4D dietary supplement appears to improve measures of cognition, specifically attention/spatial awareness, but not reaction time or reactive agility. Future research should examine the effects of this supplement with a larger, less heterogeneous sample and/or in conjunction with an exercise intervention.

Abstract The rice water weevil, Oryzophagus oryzae (Coleoptera: Curculionidae), is an economically important pest of flooded rice paddies throughout South America, and species with similar life histories are present in many rice-producing regions globally (collectively referred to here as RWWs). Plant resistance is a key strategy for management of RWWs; however, the mechanisms responsible for rice resistance to RWWs are poorly understood. We investigated morphoanatomical and biochemical plant traits potentially involved in rice resistance to O. oryzae. Resistance-associated traits were characterized in two cultivars, ‘Dawn’ (resistant) and ‘BRS Pampa CL’ (‘Pamp’ = susceptible), which were selected from among six cultivars on 2-year field screenings. Anatomical and morphological traits of leaf tissues from ‘Pamp’ and ‘Dawn’ were similar, which perhaps explains the lack of antixenosis during host plant selection. However, significant antibiosis effects were found. The activities of antioxidant enzymes involved in plant defense, as well the content of hydroxycinnamic and hydroxybenzoic acids derivatives and lignin, were higher in roots of ‘Dawn’ than in ‘Pamp’, over the period of larval infestation in the field. Additionally, ‘Dawn’ exhibited a root sclerenchyma arranged in three layers of lignified cells, which differed from the arrangement of cells in ‘Pamp’, regardless of larval infestation. Our results provide the first evidence for specific resistance-related traits associated with mortality and malnutrition of RWWs in rice.

Plain English summary The goal of comparative clinical effectiveness research is to compare healthcare options and learn which work best for patients depending on their preferences and circumstances. Research efforts can be more effective when researchers engage stakeholders, such as patients, healthcare providers, and other members of the community—especially those communities or groups targeted by the planned research. Stakeholders can give their input throughout the research process to make sure the study will address questions and concerns that are most important and useful for participants. In 2014, the PCORI funded eight research studies that evaluated various ways to help African Americans and Hispanics/Latinos with poorly controlled asthma. These groups are underrepresented in asthma research but have higher rates of and more severe asthma for reasons that are poorly understood. The goal of this report is to show how stakeholders—including patients with asthma from these underrepresented groups, healthcare providers who care for patients with asthma, key representatives from the communities and others—participated as full partners in the eight studies and helped to improve the overall quality of the research and the relationship between the researchers and the community.

The presence of and request for assistance, service, and support animals has skyrocketed on college campuses in recent years. The purpose of this literature review is to explore potential benefits in the utilization of assistance animals within higher education, especially as it concerns disability service offices. It begins with an overview of the dilemma of increased use of animals with limited shared knowledge base on the benefits of that use and the myriad of terms that are used to describe the therapeutic use of animals. It reviews relevant meta-analyses, moves to a focus of assistance animals in educational settings, especially with college students, highlighting the limited available information on the use of animals by university offices, especially the disability service office. Strength of the research in this literature review is limited due to narrow research availability, small sample sizes, qualitative methods employed in some of the studies, and the limited connections specifically to the dilemmas faced by disability offices in their decision-making about therapeutic animals. This paper concludes with recommendations for future research and for practitioners in disability service offices and related areas.

Introduction: Sacrococcygeal teratomas are typically benign tumors containing endoderm, mesoderm, and ectoderm derived tissues. They are the most common extragonadal fetal tumor and arise from the sacrococcygeal junction. These tumors can have varying levels of intrapelvic involvement, which serves as the basis for their classification system. Case presentation: This case report describes the interesting prenatal and postnatal course of a newborn with a sacrococcygeal teratoma, identified at 24 weeks via ultrasound, which underwent in utero autoamputation. Ultrasound at 34 weeks gestation revealed the teratoma freely floating in the uterine cavity. The patient was delivered via cesarean section at full term, along with the teratoma. Postnatal spinal ultrasound and MRI revealed a remaining intrapelvic portion of the mass which required surgical resection. Approximately 15 months post resection, the patient's surveillance AFP level was elevated. Cross sectional imaging revealed a 5cm solid mass in the presacral space. The patient ultimately received chemotherapy and additional resection for recurrence. Conclusion: Sacrococcygeal teratomas are a common fetal tumor with varying presentations documented in the literature. The most common presentation is a sacral mass, with variations dependent on size, location, and extension of the tumor. Our patient's presentation of a type I tumor undergoing in utero autoamputation is believed to be the first of its kind. Alternatively, our case could possibly be a yet undescribed mechanism for type IV tumors, which have no external component.

Summary: West Nile virus (WNV), the most prevalent arthropod-borne virus (arbovirus) in the United States, is maintained in a cycle between Culex spp. mosquitoes and birds. Arboviruses exist within hosts and vectors as a diverse set of closely related genotypes. In theory, this genetic diversity can facilitate adaptation to distinct environments during host cycling, yet host-specific fitness of minority genotypes has not been assessed. Utilizing WNV deep-sequencing data, we previously identified a naturally occurring, mosquito-biased substitution, NS3 P319L. Using both cell culture and experimental infection in natural hosts, we demonstrated that this substitution confers attenuation in vertebrate hosts and increased transmissibility by mosquitoes. Biochemical assays demonstrated temperature-sensitive ATPase activity consistent with host-specific phenotypes. Together these data confirm the maintenance of host-specific minority variants in arbovirus mutant swarms, suggest a unique role for NS3 in viral fitness, and demonstrate that intrahost sequence data can inform mechanisms of host-specific adaptation.

Summary: A healthy heart adapts to changes in nutrient availability and energy demands. In metabolic diseases like type 2 diabetes (T2D), increased reliance on fatty acids for energy production contributes to mitochondrial dysfunction and cardiomyopathy. A principal regulator of cardiac metabolism is 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2), which is a central driver of glycolysis. We hypothesized that increasing PFK-2 activity could mitigate cardiac dysfunction induced by high-fat diet (HFD). Wild type (WT) and cardiac-specific transgenic mice expressing PFK-2 (GlycoHi) were fed a low fat or HFD for 16 weeks to induce metabolic dysfunction. Metabolic phenotypes were determined by measuring mitochondrial bioenergetics and performing targeted quantitative proteomic and metabolomic analysis. Increasing cardiac PFK-2 had beneficial effects on cardiac and mitochondrial function. Unexpectedly, GlycoHi mice also exhibited sex-dependent systemic protection from HFD, including increased glucose homeostasis. These findings support improving glycolysis via PFK-2 activity can mitigate mitochondrial and functional changes that occur with metabolic syndrome.

Conservation alternatives that include no-tillage (NT) and cover crops (CCs) reduce soil erosion in row-crop agroecosystems. However, little information is available about how these alternatives affect soil textural properties responsible for soil fertility. This study evaluated the soil particle size distribution and volumetric water content after three years of consistent management in a raised bed system. There were four treatment systems in a dryland maize/soybean rotation on a silt loam soil (Oxyaquic Fraglossudalfs) that included: NT + CCs, conventional tillage (CT) + CCs, CT + winter weeds, and CT + bare soil in winter in northwest Mississippi. The NT + CC system retained 62% more coarse sand in the furrow than the other systems (2.1% compared to 1.3%; p = 0.02). Regardless of the location, the NT + CC system (2.5%) retained 39% more fine sand than the CT + CC system (1.8%; p = 0.01), suggesting that coarse and fine sands were being trapped in furrows combining NT + CC systems, minimizing their off-site transport. In furrows, CCs increased soil volumetric water content by 47% compared to other winter covers. In beds, NT + CCs increased bed water contents by 20% compared to CT + CCs (17.1 to 14.3%; p < 0.01). Implementing conservation alternatives may promote the retention of sand fractions in silty loam soils that are important in supporting soil fertility and crop sustainability.

Combat sports athletes seeking a competitive edge often engage in weight management practices to become larger than their opponents, which ultimately includes periods of gradual weight loss, rapid weight loss, and weight regain. This pattern of weight loss and regain is known as weight cycling and often includes periods of low energy availability, making combat sports athletes susceptible to metabolic dysfunction. This narrative review represents an effort to explore the metabolic perturbations associated with weight cycling and outline the short-, medium-, and long-term effects on metabolic flexibility, function, and health. The short-term effects of rapid weight loss, such as a reduced metabolic rate and alterations to insulin and leptin levels, may prelude the more pronounced metabolic disturbances that occur during weight regain, such as insulin resistance. Although definitive support is not currently available, this cycle of weight loss and regain and associated metabolic changes may contribute to metabolic syndrome or other metabolic dysfunctions over time.

Age-related macular degeneration (AMD) has recently been linked to cognitive impairment. We hypothesized that AMD modifies the brain aging trajectory, and we conducted a longitudinal diffusion MRI study on 40 participants (20 with AMD and 20 controls) to reveal the location, extent, and dynamics of AMD-related brain changes. Voxel-based analyses at the first visit identified reduced volume in AMD participants in the cuneate gyrus, associated with vision, and the temporal and bilateral cingulate gyrus, linked to higher cognition and memory. The second visit occurred 2 years after the first and revealed that AMD participants had reduced cingulate and superior frontal gyrus volumes, as well as lower fractional anisotropy (FA) for the bilateral occipital lobe, including the visual and the superior frontal cortex. We detected faster rates of volume and FA reduction in AMD participants in the left temporal cortex. We identified inter-lingual and lingual–cerebellar connections as important differentiators in AMD participants. Bundle analyses revealed that the lingual gyrus had a lower streamline length in the AMD participants at the first visit, indicating a connection between retinal and brain health. FA differences in select inter-lingual and lingual cerebellar bundles at the second visit showed downstream effects of vision loss. Our analyses revealed widespread changes in AMD participants, beyond brain networks directly involved in vision processing.

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Mitochondria are essential regulators of cellular energy and metabolism, and have a crucial role in sustaining the growth and survival of cancer cells. A central function of mitochondria is the synthesis of ATP by oxidative phosphorylation, known as mitochondrial bioenergetics. Mitochondria maintain oxidative phosphorylation by creating a membrane potential gradient that is generated by the electron transport chain to drive the synthesis of ATP1. Mitochondria are essential for tumour initiation and maintaining tumour cell growth in cell culture and xenografts2,3. However, our understanding of oxidative mitochondrial metabolism in cancer is limited because most studies have been performed in vitro in cell culture models. This highlights a need for in vivo studies to better understand how oxidative metabolism supports tumour growth. Here we measure mitochondrial membrane potential in non-small-cell lung cancer in vivo using a voltage-sensitive, positron emission tomography (PET) radiotracer known as 4-[18F]fluorobenzyl-triphenylphosphonium (18F-BnTP)4. By using PET imaging of 18F-BnTP, we profile mitochondrial membrane potential in autochthonous mouse models of lung cancer, and find distinct functional mitochondrial heterogeneity within subtypes of lung tumours. The use of 18F-BnTP PET imaging enabled us to functionally profile mitochondrial membrane potential in live tumours.

Multiple organizations around the world have issued evidence-based exercise guidance for patients with cancer and cancer survivors. Recently, the American College of Sports Medicine has updated its exercise guidance for cancer prevention as well as for the prevention and treatment of a variety of cancer health-related outcomes (eg, fatigue, anxiety, depression, function, and quality of life). Despite these guidelines, the majority of people living with and beyond cancer are not regularly physically active. Among the reasons for this is a lack of clarity on the part of those who work in oncology clinical settings of their role in assessing, advising, and referring patients to exercise. The authors propose using the American College of Sports Medicine's Exercise Is Medicine initiative to address this practice gap. The simple proposal is for clinicians to assess, advise, and refer patients to either home-based or community-based exercise or for further evaluation and intervention in outpatient rehabilitation. To do this will require care coordination with appropriate professionals as well as change in the behaviors of clinicians, patients, and those who deliver the rehabilitation and exercise programming. Behavior change is one of many challenges to enacting the proposed practice changes. Other implementation challenges include capacity for triage and referral, the need for a program registry, costs and compensation, and workforce development. In conclusion, there is a call to action for key stakeholders to create the infrastructure and cultural adaptations needed so that all people living with and beyond cancer can be as active as is possible for them.

Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by a few dominant species or rely on high richness remains unclear. Using a global database from 89 studies (with 1475 locations), we partition the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change. Pollinator and enemy richness directly supported ecosystem services in addition to and independent of abundance and dominance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society.

Contextual threat learning is often associated with two processes: elemental and configural learning. Few studies have examined configural learning where subjects form a representation of the threat-related context as a gestalt whole from the individual features in the environment. The goal of the current study was to compare and contrast neural circuitry recruited by variation in demands placed on configural threat encoding. Subjects (N = 25) completed a configural threat learning task, where we manipulated the amount of configural encoding required to learn the threat association (low demand: changes to a discrete element of the context; and high demand: rearrangement of elements). US expectancy ratings, skin conductance responses (SCR), and functional magnetic resonance imaging (fMRI) were collected. Subjects successfully learned the configural threat association as measured by US expectancy ratings, SCR, and BOLD activity. Hippocampal and amygdala region of interest analyses indicated differential configural threat learning and predicted SCR measures of learning. Furthermore, whole brain analyses identified four circuits that were impacted by the amount of differential configural encoding required, but none correlated with SCR. These results set the stage for a more detailed understanding of how configural threat learning is instantiated in the brain-an important mechanism associated with PTSD and other fear-related disorders.

Adipose tissue inflammation and dysfunction are associated with obesity-related insulin resistance and diabetes, but mechanisms underlying this relationship are unclear. Although senescent cells accumulate in adipose tissue of obese humans and rodents, a direct pathogenic role for these cells in the development of diabetes remains to be demonstrated. Here, we show that reducing senescent cell burden in obese mice, either by activating drug-inducible "suicide" genes driven by the p16Ink4a promoter or by treatment with senolytic agents, alleviates metabolic and adipose tissue dysfunction. These senolytic interventions improved glucose tolerance, enhanced insulin sensitivity, lowered circulating inflammatory mediators, and promoted adipogenesis in obese mice. Elimination of senescent cells also prevented the migration of transplanted monocytes into intra-abdominal adipose tissue and reduced the number of macrophages in this tissue. In addition, microalbuminuria, renal podocyte function, and cardiac diastolic function improved with senolytic therapy. Our results implicate cellular senescence as a causal factor in obesity-related inflammation and metabolic derangements and show that emerging senolytic agents hold promise for treating obesity-related metabolic dysfunction and its complications.

Predictability of behavior is an important characteristic in many fields including biology, medicine, marketing, and education. When a sequence of actions performed by an individual can be modeled as a stationary time-homogeneous Markov chain the predictability of the individual’s behavior can be quantified by the entropy rate of the process. This article compares three estimators of the entropy rate of finite Markov processes. The first two methods directly estimate the entropy rate through estimates of the transition matrix and stationary distribution of the process. The third method is related to the sliding-window Lempel–Ziv compression algorithm. The methods are compared via a simulation study and in the context of a study of interactions between mothers and their children.

To improve the translational predictability of treatment strategies for Huntington's disease (HD), sensitive and analogous cognitive outcomes are needed across HD animal models and humans. Spatial memory measures are promising candidates because they are based on 'visual' or 'non-verbal' cognition, and are commonly tested in both animals and humans. Here, we consider the suitability of spatial memory for strengthening translational links between animals and humans in HD research and clinical trials. We describe findings of spatial memory impairments in human HD and mouse models, including which aspects of spatial memory are most affected and at which time points in disease progression. We also describe the neural systems that underlie spatial memory and link spatial memory impairments to HD neuropathology, focussing on striatal and hippocampal systems. We provide a critical analysis of the literature in terms of the suitability of spatial memory for bridging the translational gap between species. Finally, we discuss possible neural mechanisms that might explain the spatial memory impairments seen in HD, and their relevance to potential treatments.