Cold-Water Immersion and Lower Limb Muscle Oxygen Consumption as Measured by Near-Infrared Spectroscopy in Trained Endurance Athletes.

CONTEXT: Cold-water immersion (CWI) has been reported to reduce tissue metabolism postimmersion, but physiological data are lacking regarding the muscle metabolic response to its application. Near-infrared spectroscopy (NIRS) is a noninvasive optical technique that can inform muscle hemodynamics and tissue metabolism. OBJECTIVE: To investigate the effects of CWI at 2 water temperatures (10°C and 15°C) on NIRS-calculated measurements of muscle oxygen consumption (mVO2). DESIGN: Crossover study. SETTING: University sports rehabilitation center. PATIENTS OR OTHER PARTICIPANTS: A total of 11 male National Collegiate Athletic Association Division II long-distance runners (age = 23.4 ± 3.4 years, height = 1.8 ± 0.1 m, mass = 68.8 ± 10.7 kg, mean adipose tissue thickness = 6.7 ± 2.7 mm). INTERVENTION(S): Cold-water immersion at 10°C and 15°C for 20 minutes. MAIN OUTCOME MEASURE(S): We calculated mVO2 preimmersion and postimmersion at water temperatures of 10°C and 15°C. Changes in tissue oxyhemoglobin (O2Hb), deoxyhemoglobin (HHb), total hemoglobin (tHb), hemoglobin difference (Hbdiff), and tissue saturation index (TSI %) were measured during the 20-minute immersion at both temperatures. RESULTS: We observed a decrease in mVO2 after immersion at both 10°C and 15°C (F1,9 = 27.7801, P = .001). During the 20-minute immersion at both temperatures, we noted a main effect of time for O2Hb (F3,27 = 14.227, P = .001), HHb (F3,27 = 5.749, P = .009), tHb (F3,27 = 24.786, P = .001), and Hbdiff (F3,27 = 3.894, P = .020), in which values decreased over the course of immersion. Post hoc pairwise comparisons showed that these changes occurred within the final 5 minutes of immersion for tHb and O2Hb. CONCLUSIONS: A 20-minute CWI at 10°C and 15°C led to a reduction in mVO2. This was greater after immersion at 10°C. The reduction in mVO2 suggests a decrease in muscle metabolic activity (ie, O2 use after CWI). Calculating mVO2 via the NIRS-occlusion technique may offer further insight into muscle metabolic responses beyond what is attainable from observing the NIRS primary signals.

Abolishment of morphology-based taxa and change to binomial species names: 2022 taxonomy update of the ICTV bacterial viruses subcommittee.

This article summarises the activities of the Bacterial Viruses Subcommittee of the International Committee on Taxonomy of Viruses for the period of March 2021-March 2022. We provide an overview of the new taxa proposed in 2021, approved by the Executive Committee, and ratified by vote in 2022. Significant changes to the taxonomy of bacterial viruses were introduced: the paraphyletic morphological families Podoviridae, Siphoviridae, and Myoviridae as well as the order Caudovirales were abolished, and a binomial system of nomenclature for species was established. In addition, one order, 22 families, 30 subfamilies, 321 genera, and 862 species were newly created, promoted, or moved.

Optimizing the Impact of Pragmatic Clinical Trials for Veteran and Military Populations: Lessons From the Pain Management Collaboratory.

Pragmatic clinical trials (PCTs) are well-suited to address unmet healthcare needs, such as those arising from the dual public health crises of chronic pain and opioid misuse, recently exacerbated by the COVID-19 pandemic. These overlapping epidemics have complex, multifactorial etiologies, and PCTs can be used to investigate the effectiveness of integrated therapies that are currently available but underused. Yet individual pragmatic studies can be limited in their reach because of existing structural and cultural barriers to dissemination and implementation. The National Institutes of Health, Department of Defense, and Department of Veterans Affairs formed an interagency research partnership, the Pain Management Collaboratory. The partnership combines pragmatic trial design with collaborative tools and relationship building within a large network to advance the science and impact of nonpharmacological approaches and integrated models of care for the management of pain and common co-occurring conditions. The Pain Management Collaboratory team supports 11 large-scale, multisite PCTs in veteran and military health systems with a focus on team science with the shared aim that the "whole is greater than the sum of the parts." Herein, we describe this integrated approach and lessons learned, including incentivizing all parties; proactively offering frequent opportunities for problem-solving; engaging stakeholders during all stages of research; and navigating competing research priorities. We also articulate several specific strategies and their practical implications for advancing pain management in active clinical, "real-world," settings.

Severe manifestations and treatment of COVID-19 in a transplanted patient with Fabry disease.

Fabry disease is an X linked disease caused by pathogenic variants in the GLA gene. The cardiovascular and renal systems are most affected in Fabry patients and may require heart or kidney transplants in the late stages of the disease depending on severity of manifestations. Enzyme replacement therapy (ERT) has proven to delay progression of Fabry disease considerably, especially when started early in life. Current research has shown that individuals who have received cardiac or renal transplants or are currently on dialysis have the greatest probability of developing severe manifestations of COVID-19. It has also been shown that people who contract COVID-19 experience a rapid increase in cytokine levels which can lead to a prothrombotic state and have a greater risk in the presence of comorbidities. A history of cardiac or renal transplants as well as the naturally elevated cytokine levels in Fabry disease make it likely that COVID-19 could have a greater impact on the health of these patients. We report the case of a 67-year-old male with diabetes mellitus, history of kidney transplant, and Fabry disease treated late in progression of the disease first with agalsidase beta ERT, then oral migalastat who developed severe manifestations of COVID-19. The autopsy findings showed acute and organizing hyaline membrane disease consistent with COVID-19 pneumonia and secondary invasive bronchopulmonary aspergillosis with cavitary lesion formation. The sections of the heart showed scattered subendocardial fibrosis, and the transplanted kidneys showed thyroidization and interstitial nephritis potentially secondary to COVID-19, in addition to his long-standing renal disease. This case report serves to chronicle complications in a complex patient with late stage Fabry disease and multiple COVID-19 related complications who succumbed from respiratory failure despite the advanced management for the COVID-19 infection.

Bacterial Viruses Subcommittee and Archaeal Viruses Subcommittee of the ICTV: update of taxonomy changes in 2021.

In this article, we - the Bacterial Viruses Subcommittee and the Archaeal Viruses Subcommittee of the International Committee on Taxonomy of Viruses (ICTV) - summarise the results of our activities for the period March 2020 - March 2021. We report the division of the former Bacterial and Archaeal Viruses Subcommittee in two separate Subcommittees, welcome new members, a new Subcommittee Chair and Vice Chair, and give an overview of the new taxa that were proposed in 2020, approved by the Executive Committee and ratified by vote in 2021. In particular, a new realm, three orders, 15 families, 31 subfamilies, 734 genera and 1845 species were newly created or redefined (moved/promoted).

Persistent Post-Mastectomy Pain: The Impact of Regional Anesthesia Among Patients with High vs Low Baseline Catastrophizing.

BACKGROUND: Persistent post-mastectomy pain (PPMP) varies both in its severity and impact, with psychosocial factors such as catastrophizing conferring greater risk. Preoperative regional anesthesia (RA) is an important nonopioid therapy, but with variable success at preventing PPMP in previous reports. We previously reported that RA was associated with lower acute post-mastectomy pain and opioid use, but more prominently among patients with higher baseline catastrophizing. The current longitudinal investigation at 3, 6, and 12 months postop aimed to detect differential long-term impact of RA on PPMP among patients with high vs low catastrophizing. METHODS: In this prospective observational study, patients (n = 123) completed preoperative psychosocial assessment and underwent mastectomy either with (n = 56) or without (n = 67) preoperative RA. Generalized estimating equation (GEE) regression analysis assessed impact of baseline catastrophizing, RA, and their interaction, on the primary outcome of pain severity index, as well as secondary outcomes including cognitive and emotional impact of pain, and persistent opioid use. RESULTS: We observed a significant interaction between the effect of catastrophizing and RA on PPMP. Specifically, RA was associated with reduced pain severity and pain impact 3, 6, and 12 months postoperatively, but only among those with high baseline catastrophizing scores. In addition, both RA and lower catastrophizing scores were associated with lower incidence of persistent opioid use. CONCLUSIONS: The efficacy of therapies to prevent PPMP may be importantly influenced by pain-modulatory psychosocial characteristics. These findings underscore the importance of considering individual patient factors when applying preventive treatments, and of including their assessment in future trials.

Prediction of Persistent Pain Severity and Impact 12 Months After Breast Surgery Using Comprehensive Preoperative Assessment of Biopsychosocial Pain Modulators.

BACKGROUND: Persistent post-mastectomy pain (PPMP) is a significant negative outcome occurring after breast surgery, and understanding which individual women are most at risk is essential to targeting of preventive efforts. The biopsychosocial model of pain suggests that factors from many domains may importantly modulate pain processing and predict the progression to pain persistence. METHODS: This prospective longitudinal observational cohort study used detailed and comprehensive psychosocial and psychophysical assessment to characterize individual pain-processing phenotypes in 259 women preoperatively. Pain severity and functional impact then were longitudinally assessed using both validated surgery-specific and general pain questionnaires to survey patients who underwent lumpectomy, mastectomy, or mastectomy with reconstruction in the first postsurgical year. An agnostic, multivariable modeling strategy identified consistent predictors of several pain outcomes at 12 months. RESULTS: The preoperative characteristics most consistently associated with PPMP outcomes were preexisting surgical area pain, less education, increased somatization, and baseline sleep disturbance, with axillary dissection emerging as the only consistent surgical variable to predict worse pain. Greater pain catastrophizing, negative affect, younger age, higher body mass index (BMI), and chemotherapy also were independently predictive of pain impact, but not severity. Sensory disturbance in the surgical area was predicted by a slightly different subset of factors, including higher preoperative temporal summation of pain. CONCLUSIONS: This comprehensive approach assessing consistent predictors of pain severity, functional impact, and sensory disturbance may inform personalized prevention of PPMP and also may allow stratification and enrichment in future preventive studies of women at higher risk of this outcome, including pharmacologic and behavioral interventions and regional anesthesia.

Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial.

ABSTRACT: Placebo effects have traditionally involved concealment or deception. However, recent evidence suggests that placebo effects can also be elicited when prescribed transparently as "open-label placebos" (OLPs), and that the pairing of an unconditioned stimulus (eg, opioid analgesic) with a conditioned stimulus (eg, placebo pill) can lead to the conditioned stimulus alone reducing pain. In this randomized control trial, we investigated whether combining conditioning with an OLP (COLP) in the immediate postoperative period could reduce daily opioid use and postsurgical pain among patients recovering from spine surgery. Patients were randomized to COLP or treatment as usual, with both groups receiving unrestricted access to a typical opioid-based postoperative analgesic regimen. The generalized estimating equations method was used to assess the treatment effect of COLP on daily opioid consumption and pain during postoperative period from postoperative day (POD) 1 to POD 17. Patients in the COLP group consumed approximately 30% less daily morphine milligram equivalents compared with patients in the treatment as usual group during POD 1 to 17 (-14.5 daily morphine milligram equivalents; 95% CI: [-26.8, -2.2]). Daily worst pain scores were also lower in the COLP group (-1.0 point on the 10-point scale; 95% CI: [-2.0, -0.1]), although a significant difference was not detected in average daily pain between the groups (-0.8 point; 95% CI: [-1.7, 0.2]). These findings suggest that COLP may serve as a potential adjuvant analgesic therapy to decrease opioid consumption in the early postoperative period, without increasing pain.

Latitude and chlorophyll a density drive the distribution of carbohydrate-active enzymes in the planktonic microbial fraction of the epipelagic zone.

Microbes drive the majority of the global carbon cycle. The effect of environmental conditions on selecting microbial functional diversity is well established, and recent studies have revealed the effects of geographic distances on selecting the functional components of marine microbial communities. Our study is the first attempt at establishing the effects of environmental factors on driving the marine carbohydrate-active enzyme (CAZyme) distribution. We characterized the diversity of CAZyme genes and investigated the correlations between their distributions and biogeographic parameters (latitude, longitude, distance from the equator, site depth, water depth, chlorophyll density, salinity and temperature). Therefore, we accessed a subset of surface water samples (38 metagenomes) from the Global Ocean Sampling project. Only chlorophyll and latitude altered the distribution patterns of CAZymes, revealing the existence of two latitudinal gradients (positive and negative) of marine CAZyme abundance. Considering the importance of carbohydrates in microbial life, characterization of the spatial patterns of the genetic repertoire involved in carbohydrate metabolism represents an important step in improving our understanding of the metabolic strategies associated with the microbial marine carbon cycle and their effects on the productivity of marine ecosystems.

Taxonomy of prokaryotic viruses: 2018-2019 update from the ICTV Bacterial and Archaeal Viruses Subcommittee.

This article is a summary of the activities of the ICTV's Bacterial and Archaeal Viruses Subcommittee for the years 2018 and 2019. Highlights include the creation of a new order, 10 families, 22 subfamilies, 424 genera and 964 species. Some of our concerns about the ICTV's ability to adjust to and incorporate new DNA- and protein-based taxonomic tools are discussed.

NCBI's Virus Discovery Hackathon: Engaging Research Communities to Identify Cloud Infrastructure Requirements.

A wealth of viral data sits untapped in publicly available metagenomic data sets when it might be extracted to create a usable index for the virological research community. We hypothesized that work of this complexity and scale could be done in a hackathon setting. Ten teams comprised of over 40 participants from six countries, assembled to create a crowd-sourced set of analysis and processing pipelines for a complex biological data set in a three-day event on the San Diego State University campus starting 9 January 2019. Prior to the hackathon, 141,676 metagenomic data sets from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) were pre-assembled into contiguous assemblies (contigs) by NCBI staff. During the hackathon, a subset consisting of 2953 SRA data sets (approximately 55 million contigs) was selected, which were further filtered for a minimal length of 1 kb. This resulted in 4.2 million (Mio) contigs, which were aligned using BLAST against all known virus genomes, phylogenetically clustered and assigned metadata. Out of the 4.2 Mio contigs, 360,000 contigs were labeled with domains and an additional subset containing 4400 contigs was screened for virus or virus-like genes. The work yielded valuable insights into both SRA data and the cloud infrastructure required to support such efforts, revealing analysis bottlenecks and possible workarounds thereof. Mainly: (i) Conservative assemblies of SRA data improves initial analysis steps; (ii) existing bioinformatic software with weak multithreading/multicore support can be elevated by wrapper scripts to use all cores within a computing node; (iii) redesigning existing bioinformatic algorithms for a cloud infrastructure to facilitate its use for a wider audience; and (iv) a cloud infrastructure allows a diverse group of researchers to collaborate effectively. The scientific findings will be extended during a follow-up event. Here, we present the applied workflows, initial results, and lessons learned from the hackathon.

Cystic Fibrosis Rapid Response: Translating Multi-omics Data into Clinically Relevant Information.

Pulmonary exacerbations are the leading cause of death in cystic fibrosis (CF) patients. To track microbial dynamics during acute exacerbations, a CF rapid response (CFRR) strategy was developed. The CFRR relies on viromics, metagenomics, metatranscriptomics, and metabolomics data to rapidly monitor active members of the viral and microbial community during acute CF exacerbations. To highlight CFRR, a case study of a CF patient is presented, in which an abrupt decline in lung function characterized a fatal exacerbation. The microbial community in the patient's lungs was closely monitored through the multi-omics strategy, which led to the identification of pathogenic shigatoxigenic Escherichia coli (STEC) expressing Shiga toxin. This case study illustrates the potential for the CFRR to deconstruct complicated disease dynamics and provide clinicians with alternative treatments to improve the outcomes of pulmonary exacerbations and expand the life spans of individuals with CF.IMPORTANCE Proper management of polymicrobial infections in patients with cystic fibrosis (CF) has extended their life span. Information about the composition and dynamics of each patient's microbial community aids in the selection of appropriate treatment of pulmonary exacerbations. We propose the cystic fibrosis rapid response (CFRR) as a fast approach to determine viral and microbial community composition and activity during CF pulmonary exacerbations. The CFRR potential is illustrated with a case study in which a cystic fibrosis fatal exacerbation was characterized by the presence of shigatoxigenic Escherichia coli The incorporation of the CFRR within the CF clinic could increase the life span and quality of life of CF patients.

Preoperative Psychosocial and Psychophysical Phenotypes as Predictors of Acute Pain Outcomes After Breast Surgery.

The severity and impact of acute pain after breast surgery varies markedly among individuals, underlining the importance of comprehensively identifying specific risk factors, including psychosocial and psychophysical traits. In this prospective observational study, women (n = 234) undergoing breast-conserving surgery, mastectomy, or mastectomy with reconstruction completed a brief bedside quantitative sensory testing battery, along with measures of psychosocial characteristics. Postoperative pain severity, impact, and opioid use at 2 weeks were assessed using Brief Pain Inventory and procedure-specific breast cancer pain questionnaires. Moderate-severe average pain (>3/10) was reported by 29% of patients at 2 weeks. Regression analysis of pain outcomes revealed that pain severity was independently predicted by axillary dissection, pre-surgical pain, temporal summation of pain (TSP), (-)positive affect, and behavioral coping style. Pain impact was predicted by age, education, axillary dissection, reconstruction, but also by negative affect and depression scores. Lastly, opioid use was predicted by age, education, axillary dissection, reconstruction, TSP, and reinterpreting coping style. Our findings suggest that, individuals with certain phenotypic characteristics, including high TSP and negative affect, may be at greater risk of significant pain and continued opioid use at 2 weeks after surgery, independent of known surgical risk factors. PERSPECTIVE: We measured differences in the psychosocial and psychophysical processing of pain amongst patients before breast surgery using simple validated questionnaires and brief quantitative sensory testing. Independent of younger age and procedural extent (axillary surgery and reconstruction), affect and greater temporal summation of pain predicted acute postoperative pain and opioid use.

A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage.

BACKGROUND: Diversity-generating retroelements (DGRs) are genetic cassettes that selectively mutate target genes to produce hypervariable proteins. First characterized in Bordetella bacteriophage BPP-1, the DGR creates a hypervariable phage tail fiber that enables host tropism switching. Subsequent surveys for DGRs conclude that the majority identified to date are bacterial or archaeal in origin. This work examines bacteriophage and bacterial genomes for novel phage-encoded DGRs. RESULTS: This survey discovered 92 DGRs that were only found in phages exhibiting a temperate lifestyle. The majority of phage-encoded DGRs were identified as prophages in bacterial hosts from the phyla Bacteroidetes, Proteobacteria, and Firmicutes. Sequence reads from these previously unidentified prophages were present in viral metagenomes (viromes), indicating these prophages can produce functional viruses. Five phages possessed hypervariable proteins with structural similarity to the tail fiber of BPP-1, whereas the functions of the remaining DGR target proteins were unknown. A novel temperate phage that harbors a DGR cassette targeting a protein of unknown function was induced from Bacteroides dorei. This phage, here named Bacteroides dorei Hankyphage, lysogenizes 13 different Bacteroides species and was present in 34% and 21% of whole-community metagenomes and human-associated viromes, respectively. CONCLUSIONS: Here, the number of known DGR-containing phages is increased from four to 92. All of these phages exhibit a temperate lifestyle, including a cosmopolitan human-associated phage. Targeted hypervariation by temperate phages may be a ubiquitous mechanism underlying phage-bacteria interaction in the human microbiome.

Chronic Pain After Breast Surgery: A Prospective, Observational Study.

BACKGROUND: Chronic pain is an important complication of breast surgery, estimated to affect 20-30% of patients. We prospectively examined surgical, demographic, and psychosocial factors associated with chronic pain 6 months after breast surgery. METHODS: Patients undergoing breast surgery for benign and malignant disease preoperatively completed validated questionnaires to assess baseline pain and psychosocial characteristics. Pain at 6 months was quantified as the Pain Burden Index (PBI), which encompasses pain locations, severity, and frequency. Surgical type was categorized as breast-conserving surgery (BCS), mastectomy, and mastectomy with reconstruction; axillary procedure was categorized as no axillary surgery, sentinel lymph node biopsy (SLNB), and axillary dissection. PBI was compared between groups using one-way analysis of variance (ANOVA) or Kruskal-Wallis ANOVA, and the relationship between baseline demographic and psychosocial factors and PBI was assessed using Spearman's Rank Correlation. p < 0.05 was considered significant. RESULTS: PBI was variable amongst patients reporting this endpoint (n = 216) at 6 months, but no difference was found between primary breast surgical types (BCS, mastectomy, and mastectomy with reconstruction) or with surgical duration. However, axillary dissection was associated with higher PBI than SLNB and no axillary procedure (p < 0.001). Younger age (< 0.001) and higher BMI (p = 0.010), as well as higher preoperative anxiety (p = 0.017), depression (p < 0.001), and catastrophizing scores (p = 0.005) correlated with higher 6-month PBI. CONCLUSIONS: Amongst surgical variables, only axillary dissection was associated with greater pain at 6 months after surgery. Patient characteristics that were associated with higher PBI included lower age and higher BMI, as well as higher baseline anxiety, depression, and catastrophizing.

Foundational and Translational Research Opportunities to Improve Plant Health.

Reader Comments | Submit a Comment The white paper reports the deliberations of a workshop focused on biotic challenges to plant health held in Washington, D.C. in September 2016. Ensuring health of food plants is critical to maintaining the quality and productivity of crops and for sustenance of the rapidly growing human population. There is a close linkage between food security and societal stability; however, global food security is threatened by the vulnerability of our agricultural systems to numerous pests, pathogens, weeds, and environmental stresses. These threats are aggravated by climate change, the globalization of agriculture, and an over-reliance on nonsustainable inputs. New analytical and computational technologies are providing unprecedented resolution at a variety of molecular, cellular, organismal, and population scales for crop plants as well as pathogens, pests, beneficial microbes, and weeds. It is now possible to both characterize useful or deleterious variation as well as precisely manipulate it. Data-driven, informed decisions based on knowledge of the variation of biotic challenges and of natural and synthetic variation in crop plants will enable deployment of durable interventions throughout the world. These should be integral, dynamic components of agricultural strategies for sustainable agriculture.

Variability and host density independence in inductions-based estimates of environmental lysogeny.

Temperate bacterial viruses (phages) may enter a symbiosis with their host cell, forming a unit called a lysogen. Infection and viral replication are disassociated in lysogens until an induction event such as DNA damage occurs, triggering viral-mediated lysis. The lysogen-lytic viral reproduction switch is central to viral ecology, with diverse ecosystem impacts. It has been argued that lysogeny is favoured in phages at low host densities. This paradigm is based on the fraction of chemically inducible cells (FCIC) lysogeny proxy determined using DNA-damaging mitomycin C inductions. Contrary to the established paradigm, a survey of 39 inductions publications found FCIC to be highly variable and pervasively insensitive to bacterial host density at global, within-environment and within-study levels. Attempts to determine the source(s) of variability highlighted the inherent complications in using the FCIC proxy in mixed communities, including dissociation between rates of lysogeny and FCIC values. Ultimately, FCIC studies do not provide robust measures of lysogeny or consistent evidence of either positive or negative host density dependence to the lytic-lysogenic switch. Other metrics are therefore needed to understand the drivers of the lytic-lysogenic decision in viral communities and to test models of the host density-dependent viral lytic-lysogenic switch.