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1.
Cureus ; 16(8): e65961, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39221308

ABSTRACT

Nicotinamide adenine dinucleotide (NAD+) is essential in the proper function of many essential cellular processes in the human body. The purpose of this review is to investigate the effect of nicotinamide mononucleotide (NMN), a NAD+ precursor, on physical performance and evaluate the safety profile of supplementation. A systematic review search criteria following the guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed in four databases for randomized controlled trials on NMN supplementation. Study variables included title, author, publication date, study year, number of patients, dosage, mean age, mean follow-up time, pre- and post-intervention reported outcomes, and rates of complications. Ten studies, including 437 patients, with a mean age of 58.0 years (35.1 to 81.1 years) and a mean follow-up time of 9.6 weeks (4 to 12 weeks) were included in this study. NMN dosages ranged from 150 to 1200 mg/day. Mean pre-intervention grip strength (two studies) and skeletal mass index (two studies) were 29.9 kilograms (kg) (range: 21.4-40.1 kg) and 7.4 kg/m2 (range: 6.9-7.65 kg/m2), respectively. Mean post-intervention grip strength and skeletal mass index were 30.5 kg (range: 21.7-41.9 kg) and 7.4 kg/m2 (6.8-7.64 kg/m2), respectively. There were no serious adverse effects observed. Moreover, of the reported side effects, they were determined to be independent of NMN supplementation. Therefore, patients taking NMN supplementation demonstrated non-significantly improved physical performance parameters. NMN is well tolerated with no serious adverse effects observed.

2.
J Chem Phys ; 161(9)2024 Sep 07.
Article in English | MEDLINE | ID: mdl-39230369

ABSTRACT

We present the development of a new astrochemical research tool, HILTRAC, the Highly Instrumented Low Temperature ReAction Chamber. The instrument is based on a pulsed form of the CRESU (Cinétique de Réaction en Écoulement Supersonique Uniforme, meaning reaction kinetics in a uniform supersonic flow) apparatus, with the aim of collecting kinetics and spectroscopic information on gas phase chemical reactions important in interstellar space or planetary atmospheres. We discuss the apparatus design and its flexibility, the implementation of pulsed laser photolysis followed by laser induced fluorescence, and the first implementation of direct infrared frequency comb spectroscopy (DFCS) coupled to the uniform supersonic flow. Achievable flow temperatures range from 32(3) to 111(9) K, characterizing a total of five Laval nozzles for use with N2 and Ar buffer gases by impact pressure measurements. These results were further validated using LIF and direct frequency comb spectroscopy measurements of the CH radical and OCS, respectively. Spectroscopic constants and linelists for OCS are reported for the 1001 band near 2890-2940 cm-1 for both OC32S and OC34S, measured using DFCS. Additional peaks in the spectrum are tentatively assigned to the OCS-Ar complex. The first reaction rate coefficients for the CH + OCS reaction measured between 32(3) and 58(5) K are reported. The reaction rate coefficient at 32(3) K was measured to be 3.9(4) × 10-10 cm3 molecule-1 s-1 and the reaction was found to exhibit no observable temperature dependence over this low temperature range.

3.
J Nutr ; 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39218399

ABSTRACT

BACKGROUND: Dietary intake has been suggested to be associated with the oral microbiome, but no study has examined the association between overall diet quality and the oral microbiome. OBJECTIVE: This study aims to investigate the cross-sectional association between the Healthy Eating Index-2020 (HEI-2020) and the diversity and composition of the oral microbiome among participants in the Buffalo Osteoporosis and Periodontal Disease (OsteoPerio) Study. METHODS: In 1,175 postmenopausal women (mean age 67±7.0 yrs), we estimated the HEI-2020 scores for each woman from a food frequency questionnaire administered from 1997-2000. Bacterial DNA was extracted from subgingival plaque samples and analyzed using 16S ribosomal RNA sequencing. The alpha-diversity (within-sample diversity) and beta-diversity (between-sample diversity) across HEI-2020 quartiles were examined using ANCOVA and PERMANOVA, respectively. The associations between the HEI-2020 score and the relative abundance of microbial taxa were examined by linear regression models. The analyses were further conducted for individual components of the HEI-2020. RESULTS: No statistically significant associations were observed between the HEI-2020 scores and the alpha- or beta-diversity. However, greater consumption of seafood and plant proteins, as well as total protein, and lower consumption of added sugars, were positively associated with alpha-diversity. After we applied a false detection rate (FDR) correction, higher HEI-2020 scores were significantly associated with decreased abundance of Lautropia, Streptococcus gordonii, Cardiobacterium valvarum, and Cardiobacterium hominis, and increased abundance of Selenomonas sp. oral taxon 133 and Selenomonas dianae (FDR adjusted p-values<0.10). Additionally, 28 other taxa were identified as being associated with HEI-2020 components. CONCLUSION: While the HEI-2020 was associated with the composition, but not the diversity, of the oral microbiome, individual HEI-2020 components were associated with both its diversity and composition. Specific dietary components may have more impact on the diversity and composition of oral microbiome than overall diet quality assessed by the HEI-2020.

4.
Br J Anaesth ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39232909

ABSTRACT

BACKGROUND: Frailty is associated with morbidity and mortality after surgery. The association of frailty with decisional regret is poorly defined. Our objective was to estimate the association of preoperative frailty with decisional regret status in the year after surgery. METHODS: We conducted a secondary analysis of a prospective, multicentre cohort study of patients aged ≥65 years who underwent elective noncardiac surgery. Decisional regret about having undergone surgery was ascertained at 30, 90, and 365 (primary time point) days after surgery using a 3-point ordinal scale. Bayesian ordinal logistic regression was used to estimate the association of frailty with decisional regret, adjusted for surgery type, age, sex, and mental health conditions. Subgroup and sensitivity analyses were conducted. RESULTS: We identified 669 patients; 293 (43.8%) lived with frailty. At 365 days after surgery, the unadjusted odds ratio (OR) associating frailty with greater decisional regret was 2.21 (95% credible interval [CrI] 0.98-5.09; P(OR>1)=0.97), which was attenuated after confounder adjustment (adjusted OR 1.68, 95% CrI 0.84-3.36; P(OR>1)=0.93). Similar results were estimated at 30 and 90 days. Additional adjustment for baseline comorbidities and disability score substantially altered the OR at 365 days (0.89, 95% CrI 0.37-2.12; P(OR>1)=0.39). There was a high probability that surgery type was an effect modifier (non-orthopaedic: OR 1.90, 95% CrI 1.00-3.59; P(OR>1)=0.98); orthopaedic: OR 0.87, 95% CrI 0.41-1.91; P(OR>1)=0.36). CONCLUSIONS: Among older surgical patients, there appears to be a complex association with frailty and decisional regret, with substantial heterogeneity based on assumed causal pathways and surgery type. Future studies are required to untangle the complex interplay between these factors.

5.
Blood ; 2024 Sep 03.
Article in English | MEDLINE | ID: mdl-39226462

ABSTRACT

Genetic studies have identified numerous regions associated with plasma fibrinogen levels in Europeans, yet missing heritability and limited inclusion of non-Europeans necessitates further studies with improved power and sensitivity. Compared with array-based genotyping, whole genome sequencing (WGS) data provides better coverage of the genome and better representation of non-European variants. To better understand the genetic landscape regulating plasma fibrinogen levels, we meta-analyzed WGS data from the NHLBI's Trans-Omics for Precision Medicine (TOPMed) program (n=32,572), with array-based genotype data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium (n=131,340) imputed to the TOPMed or Haplotype Reference Consortium panel. We identified 18 loci that have not been identified in prior genetic studies of fibrinogen. Of these, four are driven by common variants of small effect with reported MAF at least 10 percentage points higher in African populations. Three signals (SERPINA1, ZFP36L2, and TLR10) contain predicted deleterious missense variants. Two loci, SOCS3 and HPN, each harbor two conditionally distinct, non-coding variants. The gene region encoding the fibrinogen protein chain subunits (FGG;FGB;FGA), contains 7 distinct signals, including one novel signal driven by rs28577061, a variant common in African ancestry populations but extremely rare in Europeans (MAFAFR=0.180; MAFEUR=0.008). Through phenome-wide association studies in the VA Million Veteran Program, we found associations between fibrinogen polygenic risk scores and thrombotic and inflammatory disease phenotypes, including an association with gout. Our findings demonstrate the utility of WGS to augment genetic discovery in diverse populations and offer new insights for putative mechanisms of fibrinogen regulation.

6.
J Environ Radioact ; 279: 107514, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39142005

ABSTRACT

The Saltstone Disposal Facility on the Savannah River Site in South Carolina disposes of Low-Level Waste in a reducing-grout waste form. Reducing grout is presently being evaluated as a subsurface disposal waste form at several other locations in the United States, as well as in Europe and Asia. The objective of this study was to collect core samples directly from the Saltstone Disposal Facility and measure desorption distribution coefficients (Kd; radionuclide concentration ratio of saltstone:liquid; (Bq/kg)/Bq/L)) and desorption apparent solubility values (ksp; radionuclide aqueous concentration (moles/L)). An important attribute of this study was that these tests were conducted with actual aged, grout waste form materials, not small-volume simulants prepared in a laboratory. The reducing grout is comprised of blast furnace slag, Class F fly ash, ordinary portland cement, and a radioactive salt waste solution generated during nuclear processing. The grout sample used in this study underwent hydrolyzation in the disposal facility for 30 months prior to measuring radionuclide leaching. Leaching experiments were conducted either in an inert (no oxygen) atmosphere to simulate conditions within the saltstone monolith prior to aging (becoming oxidized) or they were exposed to atmosphere conditions to simulate conditions of an aged saltstone. Importantly, these experiments were designed not to be diffusion limited, that is, the saltstone was ground finely and the suspensions were under constant agitation during the equilibration period. Under oxidized conditions, measured Tc Kd values were 10 mL/g, which was appreciably greater than the historical best-estimate value of 0.8 mL/g. This difference is likely the result of a fraction of the Tc remaining in the less soluble Tc(IV) form, even after extensive oxidation during the experiment. Under oxidized and reducing conditions, the measured Ba and Sr (both divalent alkaline earth metals) Kd value were more than an order of magnitude greater than historical best-estimate values of 100 mL/g. The unexpectedly high Ba and Sr Kd values were attributed to these radionuclides having sufficient time to age (form strong bonds) in the sulfur-rich saltstone sample. Apparent ksp values under reducing conditions were 10-9 mol/L Tc and 10-13 mol/L Pu, consistent with values measured with surrogate materials. Measured apparent Ba, Sr, and Th ksp values were significantly greater than historical best-estimates. The implications of the generally greater Kd values and lower ksp values in these measurements is that these cementitious waste forms have greater radionuclide retention than was previously estimated based on laboratory studies using surrogate materials. This work represents the first leaching study performed with an actual aged, reducing-grout sample and as such provides an important comparison to studies conducted with surrogate materials, and provides high pedigree data for other programs around the world evaluating reducing grouts as a wasteform for subsurface nuclear waste disposal.

7.
J Am Coll Radiol ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39142545

ABSTRACT

OBJECTIVE: To determine the volume of intravenous iodinated contrast media utilized for CT before, during, and after the global iohexol shortage over a total of 17 months at a multisite health system. METHODS: This retrospective study included all patients who underwent CT at a large health system with 12 sites. Standardized contrast doses for 13 CT examinations were implemented 5/23/22. Mean contrast utilization per CT encounter was compared between 3 periods (pre-intervention 1/1/22-5/22/22; intervention 5/23/22-9/11/22; post-intervention 9/12/23-6/30/23). Contrast doses and CT encounter data were extracted from the enterprise data warehouse. Categorical variables were compared with a chi-squared test and continuous variables were compared with a two-tailed t-test. Multivariable linear regression assessed significance, with coefficients noted to determine magnitude and direction of effect. RESULTS: Pre-intervention, there were 152,009 examinations (87,722 with contrast, 57.7%), during the intervention 120,031 examinations (63,217 with contrast, 52.7%), and post-intervention 341,862 examinations (194,231 with contrast, 56.8%). Pre-intervention, mean contrast dose was 89.3 mL per exam, which decreased to 78.0 mL following standardization (Δ of -12.7%) (p<0.001). This decrease continued throughout the intervention and persisted in the post-intervention period (80.4 mL; Δ -10.0%, p<0.001). On multivariable analysis, patient weight, sex, and performing site were all associated with variations in contrast dose. Most but not all sites (9/12) sustained the decreased contrast media dose in the post-intervention period. DISCUSSION: Implementing standardized contrast media dosing for commonly performed CT examinations led to a rapid decrease in contrast media utilization which persisted over 1 year.

8.
Cureus ; 16(7): e64033, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39114194

ABSTRACT

Background This study aims to investigate the potential association of the Chief Executive Officer (CEO)'s educational background on hospital safety metrics, specifically the Leapfrog safety grades. Methods A total of 172 academic and university-affiliated hospitals across the United States were included in the study. Information regarding a CEO's background was obtained through hospital websites, while the Leapfrog safety scores were found through the Leapfrog safety grade website. Hospital sizes were also noted. Results A total of 67 hospitals were led by Doctors of Medicine (MDs), 16 were led by Masters in Business Administration (MBAs), 14 were led by Masters in Healthcare Administration (MHAs), and 62 were led by CEOs with various other degree types. Of the 42 A-rated hospitals included, 17 were led by physicians and 25 by nonphysicians. The average Leapfrog grade point average was similar regardless of the CEO's background, ranging from 2.6 to 3.1. Conclusion The findings suggest that a CEO's educational background has less of an impact on the overall hospital safety performance than what may have previously been hypothesized.

10.
JACC Heart Fail ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39115521

ABSTRACT

BACKGROUND: For patients with acute heart failure (HF), specialist HF care during admission improves diagnosis and treatments. OBJECTIVES: The authors aimed to investigate the association of HF specialist care with in-hospital and longer term prognosis. METHODS: The authors used data from the National Heart Failure Audit from January 1, 2018, to December 31, 2022, linked to electronic records for hospitalization and deaths. All-cause mortality was the primary outcome measure and in-hospital mortality the secondary outcome measure. RESULTS: Data for 227,170 patients admitted to hospital with HF (median age: 81 years; IQR: 72-88 years), were analyzed. Approximately 80% of acute HF admissions received support from HF specialists. Thirty-nine percent of patients (n = 70,720) were seen by a multidisciplinary team (HF physicians and HF specialist nurses [HFSNd]), 22% (n = 40,330) were seen by HFSNs alone, and the remaining 39% (n = 71,700) were seen exclusively by specialist HF physicians. At discharge, more patients who received HF specialist care were prescribed medical therapy for HF and had specialized follow-up. Conversely, diuretic agents were prescribed to fewer patients. HF specialist care was independently associated with a higher rate of prescribing HF therapies at discharge and a lower likelihood of receiving diuretic therapy (OR: 0.90 [95% CI: 0.86-0.95]; P < 0.001). HF specialist care was associated with better long-term survival (HR: 0.89 [95% CI: 0.87-0.90]; P < 0.001) and lower in-hospital mortality (OR: 0.92 [95% CI: 0.0.88-0.97]; P < 0.001). CONCLUSIONS: Receiving HF specialist care during admission for HF is associated with a higher rate of implementation of medical therapy, fewer discharges on diuretic therapy, and lower in-hospital and long-term mortality across the left ventricular ejection fraction spectrum, especially for patients with heart failure with reduced ejection fraction.

11.
Allergy ; 2024 Aug 04.
Article in English | MEDLINE | ID: mdl-39099223

ABSTRACT

The impact of human IgE glycosylation on structure, function and disease mechanisms is not fully elucidated, and heterogeneity in different studies renders drawing conclusions challenging. Previous reviews discussed IgE glycosylation focusing on specific topics such as health versus disease, FcεR binding or impact on function. We present the first systematic review of human IgE glycosylation conducted utilizing the PRISMA guidelines. We sought to define the current consensus concerning the roles of glycosylation on structure, biology and disease. Despite diverse analytical methodologies, source, expression systems and the sparsity of data on IgE antibodies from non-allergic individuals, collectively evidence suggests differential glycosylation profiles, particularly in allergic diseases compared with healthy states, and indicates functional impact, and contributions to IgE-mediated hypersensitivities and atopic diseases. Beyond allergic diseases, dysregulated terminal glycan structures, including sialic acid, may regulate IgE metabolism. Glycan sites such as N394 may contribute to stabilizing IgE structure, with alterations in these glycans likely influencing both structure and IgE-FcεR interactions. This systematic review therefore highlights critical IgE glycosylation attributes in health and disease that may be exploitable for therapeutic intervention, and the need for novel analytics to explore pertinent research avenues.

12.
Front Toxicol ; 6: 1393330, 2024.
Article in English | MEDLINE | ID: mdl-39109300

ABSTRACT

Engineered nanoparticles (NPs) pose a broad spectrum of interesting properties that make them useful for many applications. However, continuous exposure to NPs requires the need to deeply understand the outcomes when these NPs interact with different biological environments. After exposure within (to) these environments, the pristine surfaces of NPs strongly interact with the molecules from the surrounding medium, including metabolites, lipids, glycan, and proteins, forming the so-called protein corona (PC). It is well established that the NP-PC strongly influences the biological fate of various NPs types, including cellular uptake, toxicity, and biodistribution. Thus, for a proper assessment of potential hazards associated with engineered NPs, it is mandatory to study and evaluate the PC that forms around NPs. Herein, we describe protocols in detail for the isolation and characterization of NP-PC complexes and cover the following aspects: 1) isolation protocols for different nanomaterials in a range of exposing media, including magnetic isolation methods for superparamagnetic NPs, 2) NP physico-chemical characterization using advanced and standard techniques available in regular laboratories, and 3) NP- PC characterization of the protein and glycan components.

13.
Skeletal Radiol ; 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39180558

ABSTRACT

OBJECTIVE: To compare the frequency of elongated morphology of osteoid osteoma (OO) in children compared to adolescents and to determine if this elongated morphology is associated with radiofrequency ablation treatment failure. MATERIALS AND METHODS: Retrospective review of first-time CT-guided radiofrequency ablation performed for presumed OO in patients < 21 years old between 1990 and 2023. Children were considered 0 to 10 years old, and adolescents were considered 11 to 20 years old. Treatment failure was considered symptomatic recurrence requiring follow-up intervention. The largest tumor dimensions in three orthogonal planes were measured using multiplanar reformatted technology. Maximum tumor dimension, tumor volume, and eccentricity index were calculated. Elongated morphology criteria were (a) largest dimension > 10 mm and (b) eccentricity index ≥ 3. Lesion locations were recorded. Statistical analyses included the chi-square test, Fisher's exact test, nonparametric Wilcoxon rank-sum test, receiver operating characteristic analysis, and Spearman's nonparametric rank correlation. RESULTS: Of 366 included patients (median 15 years, IQR 11-18 years, 254 male), there were 86 (23.5%) children, 280 (76.5%) adolescents, and 24 (6.6%) cases of treatment failure. Elongated morphology was more common in children (19.7%) than adolescents (8.6%) (p = 0.004) and associated with younger age (p = 0.009). Elongated morphology was associated with treatment failure in children (p = 0.045) but not adolescents (p > .99) or all patients (p = 0.17). Treatment failure was not associated with age, largest dimension, eccentricity index, volume, or location. CONCLUSION: Elongated morphology of OO is associated with younger age and radiofrequency ablation treatment failure in children. Identifying this morphology may assist with counseling and treatment planning.

14.
bioRxiv ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39149263

ABSTRACT

Commensal oral streptococci that colonize supragingival biofilms deploy mechanisms to combat competitors within their niche. Here, we determined that Streptococcus mitis more effectively inhibited biofilm formation of Streptococcus mutans within a seven species panel. This phenotype was common amongst all assayed isolates of S. mutans, but was specific to a single strain of S. mitis, ATCC 49456. The growth inhibitory factor was not effectively carried in spent supernatants of S. mitis. However, we documented ATCC 49456 to accumulate 4-5 times more hydrogen peroxide (H2O2) than other species tested, and 5-18 times more than other S. mitis strains assayed. The S. mutans biofilm formation inhibitory phenotype was reduced when grown in media containing catalase or with a S. mitis mutant of pyruvate oxidase (spxB; pox), confirming that SpxB-dependent H2O2 production was the main antagonistic factor. Addition of S. mitis within hours after S. mutans inoculation was effective at reducing biofilm biomass, but not for 24 h pre-formed biofilms. Transcriptome analysis revealed responses for both S. mitis and S. mutans, with several S. mutans differentially expressed genes following a gene expression pattern previously described, while others being unique to the interaction with S. mitis. Finally, we show that S. mitis also affected coculture biofilm formation of several other commensal streptococci. Our study shows that strains with abundant H2O2 production are effective at inhibiting initial growth of caries pathogens like S. mutans, but are less effective at disrupting pre-formed biofilms and have the potential to influence the stability of other oral commensal strains.

15.
Nat Commun ; 15(1): 6941, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39138162

ABSTRACT

Glucagon-like peptide 1 (GLP-1) stimulates insulin secretion and holds significant pharmacological potential. Nevertheless, the regulation of energy homeostasis by centrally-produced GLP-1 remains partially understood. Preproglucagon cells, known to release GLP-1, are found in the olfactory bulb (OB). We show that activating GLP-1 receptors (GLP-1R) in the OB stimulates insulin secretion in response to oral glucose in lean and diet-induced obese male mice. This is associated with reduced noradrenaline content in the pancreas and blocked by an α2-adrenergic receptor agonist, implicating functional involvement of the sympathetic nervous system (SNS). Inhibiting GABAA receptors in the paraventricular nucleus of the hypothalamus (PVN), the control centre of the SNS, abolishes the enhancing effect on insulin secretion induced by OB GLP-1R. Therefore, OB GLP-1-dependent regulation of insulin secretion relies on a relay within the PVN. This study provides evidence that OB GLP-1 signalling engages a top-down neural mechanism to control insulin secretion via the SNS.


Subject(s)
Glucagon-Like Peptide 1 , Glucagon-Like Peptide-1 Receptor , Insulin Secretion , Mice, Inbred C57BL , Olfactory Bulb , Paraventricular Hypothalamic Nucleus , Animals , Glucagon-Like Peptide 1/metabolism , Male , Olfactory Bulb/metabolism , Olfactory Bulb/drug effects , Insulin Secretion/drug effects , Glucagon-Like Peptide-1 Receptor/metabolism , Mice , Paraventricular Hypothalamic Nucleus/metabolism , Insulin/metabolism , Obesity/metabolism , Sympathetic Nervous System/metabolism , Neurons/metabolism , Signal Transduction , Norepinephrine/metabolism , Glucose/metabolism
16.
R Soc Open Sci ; 11(6): 231571, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39100184

ABSTRACT

A crop boom is a sudden, nonlinear and intense expansion of a new crop. Despite their large impacts, boom-bust dynamics are not well understood; booms are largely unpredictable and difficult to steer once they unfold. Based on the striking resemblances between land regime shifts and crop booms, we apply complex systems theory, highlighting the potential for regime shifts, to provide new insights about crop boom dynamics. We analyse qualitative and quantitative data of rubber and banana plantation expansion in two forest frontier regions of northern Laos. We show that preconditions, including previous booms, explain the occurrence (why) of booms, and triggers like policy and market changes explain their timing (when). Yet, the most important features of booms, their intensity and nonlinearity (how), strongly depended on internal self-reinforcing feedbacks. We identify built-in feedbacks (neighbourhood effects and imitation) and emergent feedbacks (land rush) and show that they were social in nature, multi-scale from plot to region and subject to thresholds. We suggest that these are regular features of booms and propose a definition and causal-mechanistic explanation of crop booms, examining the overlap between booms and regime shifts and the role of frontiers. We then identify opportunities for management interventions before, during and after booms.

17.
Article in English | MEDLINE | ID: mdl-39096759

ABSTRACT

Among terrestrial ectotherms, hibernation is a common response to extreme cold temperatures and is associated with reduced physiological rates, including immunity. When winter wanes and temperatures increase, so too do vital rates of both ectothermic hosts and their parasites. Due to metabolic scaling, if parasite activity springs back faster than host immune functions then cold seasons and transitions between cold and warm seasons may represent periods of vulnerability for ectothermic hosts. Understanding host regulation of physiological rates at seasonal junctions is a first step toward identifying thermal mismatches between hosts and parasites. Here we show that immune gene expression is responsive to transitions into and out of the cold season in a winter-adapted amphibian, the wood frog (Lithobates sylvaticus), and that frogs experienced parasitism by at least two nematode species throughout the entirety of the cold season. In both splenic and skin tissues, we observed a decrease in immune gene expression going from fall to winter, observed no changes between winter and emergence from hibernation, and observed increases in immune gene expression after hibernation ended. At all timepoints, differentially expressed genes from spleens were more highly enriched for immune system processes than those from ventral skin, especially with respect to terms related to adaptive immune processes. Infection with nematode lungworms was also associated with upregulation of immune processes in the spleen. We suggest that rather than being a period of stagnation, during which physiological processes and infection potential cease, the cold season is immunologically dynamic, requiring coordinated regulation of many biological processes, and that the reemergence period may be an important time during which hosts invest in preparatory immunity.

18.
Appl Environ Microbiol ; : e0059924, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39133000

ABSTRACT

Leptothrix ochracea creates distinctive iron-mineralized mats that carpet streams and wetlands. Easily recognized by its iron-mineralized sheaths, L. ochracea was one of the first microorganisms described in the 1800s. Yet it has never been isolated and does not have a complete genome sequence available, so key questions about its physiology remain unresolved. It is debated whether iron oxidation can be used for energy or growth and if L. ochracea is an autotroph, heterotroph, or mixotroph. To address these issues, we sampled L. ochracea-rich mats from three of its typical environments (a stream, wetlands, and a drainage channel) and reconstructed nine high-quality genomes of L. ochracea from metagenomes. These genomes contain iron oxidase genes cyc2 and mtoA, showing that L. ochracea has the potential to conserve energy from iron oxidation. Sox genes confer potential to oxidize sulfur for energy. There are genes for both carbon fixation (RuBisCO) and utilization of sugars and organic acids (acetate, lactate, and formate). In silico stoichiometric metabolic models further demonstrated the potential for growth using sugars and organic acids. Metatranscriptomes showed a high expression of genes for iron oxidation; aerobic respiration; and utilization of lactate, acetate, and sugars, as well as RuBisCO, supporting mixotrophic growth in the environment. In summary, our results suggest that L. ochracea has substantial metabolic flexibility. It is adapted to iron-rich, organic carbon-containing wetland niches, where it can thrive as a mixotrophic iron oxidizer by utilizing both iron oxidation and organics for energy generation and both inorganic and organic carbon for cell and sheath production. IMPORTANCE: Winogradsky's observations of L. ochracea led him to propose autotrophic iron oxidation as a new microbial metabolism, following his work on autotrophic sulfur-oxidizers. While much culture-based research has ensued, isolation proved elusive, so most work on L. ochracea has been based in the environment and in microcosms. Meanwhile, the autotrophic Gallionella became the model for freshwater microbial iron oxidation, while heterotrophic and mixotrophic iron oxidation is not well-studied. Ecological studies have shown that Leptothrix overtakes Gallionella when dissolved organic carbon content increases, demonstrating distinct niches. This study presents the first near-complete genomes of L. ochracea, which share some features with autotrophic iron oxidizers, while also incorporating heterotrophic metabolisms. These genome, metabolic modeling, and transcriptome results give us a detailed metabolic picture of how the organism may combine lithoautotrophy with organoheterotrophy to promote Fe oxidation and C cycling and drive many biogeochemical processes resulting from microbial growth and iron oxyhydroxide formation in wetlands.

19.
Anesthesiology ; 141(3): 428-430, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39136483
20.
Addict Behav ; 158: 108133, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39163696

ABSTRACT

OBJECTIVE: Study of the association between smoking and pain intensity has produced conflicting results; with less focus on pain interference. Different pain constructs could have varying associations with smoking behaviors. This study sought to investigate the association between smoking history and not only pain intensity, but also pain interference, symptom distribution and physical function. METHODS: Smoking history (current, past, or none), pain interference (Pain, Enjoyment of Life, and General Activity scale), symptom distribution and physical function scores were extracted from medical records of patients seen in physical therapy for common sites of musculoskeletal pain (lumbar and cervical spine, knee, or hip). Generalized linear models assessed the relationship between smoking history and pain/function. RESULTS: 833 patients from an integrated healthcare system were included (mean: 57.6 years, SD=16.3; 43 % male). After controlling for several variables, current smokers had significantly higher baseline pain interference scores compared to never and former smokers (beta [B]: 0.65, 95 %CI: 0.13 to 1.18, P=.02). Smoking was not a significant predictor of symptom distribution at baseline [B: 0.17, 95 %CI -0.06 to 0.42, P=.16] or physical function scores at discharge [B: -0.03, 95 %CI: -0.08 to 0.02, P=.25]. CONCLUSION: Smokers experienced a greater impact of pain at baseline. However, symptom distribution at intake and function upon discharge were similar between all smoking groups. These findings suggest smoking cessation and abstinence may be important recommendations to help curb pain interference.


Subject(s)
Musculoskeletal Pain , Smoking , Humans , Male , Female , Middle Aged , Musculoskeletal Pain/therapy , Musculoskeletal Pain/psychology , Smoking/psychology , Smoking/epidemiology , Adult , Aged , Patient Discharge/statistics & numerical data , Pain Measurement
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