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1.
Osteoporos Int ; 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38890177

RESUMEN

Evidence regarding the risk factors and characteristics of those with foot fragility fractures compared to non-foot fragility fractures is limited. Foot fragility fracture patients are more likely to be younger female with a higher BMI. A foot fragility fracture is strongly predictive of a subsequent foot fragility fracture. PURPOSE: Osteoporosis can clinically result in fragility fractures. Evidence regarding the risk factors and characteristics of foot fragility fractures compared to non-foot fragility fractures is limited. The American Orthopaedic Association's Own the Bone (OTB) is a bone health initiative with a substantial dataset. The purpose of this study was to examine and compare characteristics of patients presenting with isolated foot fragility fracture to those with a non-foot fragility fracture. METHODS: Between January 2009 and March of 2022, 58,001 fragility fractures occurred that were included in this cohort. A total of 750 patients had foot fragility fracture(s) and 57,251 patients had a non-foot fragility fracture that included shoulder, arm, elbow, forearm, wrist, spine, ribs, pelvis, hip, thigh, knee, tibia/fibula, and ankle. Demographics, fracture history, bone health factors, medication history, and medication use for each patient were reported in the OTB database. This data was utilized in our secondary cohort comparative analysis of characteristics and the risk of future fractures between foot fragility fracture and non-foot fragility fracture groups. RESULTS: Foot fragility fracture patients have a significantly higher probability to be younger (66.9 years old), female (91.5%), and have a higher BMI (28.3 kg/m2) compared to non-foot fragility fracture (p < 0.0001) patients. Patients with a foot fragility fracture are nine times (OR = 9.119, CI = 7.44-11.18, p < 0.001) more likely to have had a prior foot fragility fracture. Young, female patients with a prior foot fragility fracture are at higher risk of a future foot fragility fracture, and this risk increased as BMI increased. CONCLUSIONS: Foot fragility fracture patients are more likely to be female and younger compared to patients with a non-foot fragility fracture. A foot fragility fracture is a sentinel event considering that a prior foot fragility fracture is strongly predictive of a subsequent foot fragility fracture. LEVEL OF EVIDENCE: 3 (retrospective cohort).

2.
J Mass Spectrom ; 59(7): e5065, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38866597

RESUMEN

Nanospray desorption electrospray ionization (nano-DESI) is an ambient ionization mass spectrometry imaging (MSI) approach that enables spatial mapping of biological and environmental samples with high spatial resolution and throughput. Because nano-DESI has not yet been commercialized, researchers develop their own sources and interface them with different commercial mass spectrometers. Previously, several protocols focusing on the fabrication of nano-DESI probes have been reported. In this tutorial, we discuss different hardware requirements for coupling the nano-DESI source to commercial mass spectrometers, such as the safety interlock, inlet extension, and contact closure. In addition, we describe the structure of our custom software for controlling the nano-DESI MSI platform and provide detailed instructions for its usage. With this tutorial, interested researchers should be able to implement nano-DESI experiments in their labs.

3.
Nat Microbiol ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38862604

RESUMEN

Maintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals. Using paired metagenomics and metatranscriptomics alongside single-nuclei immune cell profiling, we characterized time-dependent, multikingdom microbiome changes across 750 samples and 10 body sites before, during and after spaceflight at eight timepoints. We found that most alterations were transient across body sites; for example, viruses increased in skin sites mostly during flight. However, longer-term shifts were observed in the oral microbiome, including increased plaque-associated bacteria (for example, Fusobacteriota), which correlated with immune cell gene expression. Further, microbial genes associated with phage activity, toxin-antitoxin systems and stress response were enriched across multiple body sites. In total, this study reveals in-depth characterization of microbiome and immune response shifts experienced by astronauts during short-term spaceflight and the associated changes to the living environment, which can help guide future missions, spacecraft design and space habitat planning.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38863419

RESUMEN

BACKGROUND: There is conflicting evidence regarding the presence and magnitude of exercise-induced muscle damage (EIMD) following low-load resistance training with blood flow restriction (LL+BFR), which may be related to the protocol implemented or exercise volume. Therefore, the purpose of this investigation was to examine the effects of a 75 repetition (BFR-75) (1×30, 3×15) and four sets to volitional failure (BFR-4x) protocols on indices of EIMD among untrained men. METHODS: Twelve males with no history of lower-body resistance training during the previous six months volunteered for this investigation. One leg was randomly assigned to BFR-75, and the other to BFR-4x. Participants performed isokinetic, unilateral, concentric-eccentric, leg extension muscle actions at 30% of maximal strength with BFR. Indices of EIMD (limb circumference, perceived muscle soreness, pain pressure threshold [PPT], passive range of motion, and maximal strength [MVIC]) were recorded before exercise and 0, 24, 48, 72, and 96-hours post-exercise for each protocol. RESULTS: There were no significant changes (P>0.05) in limb circumference, PPT, passive range of motion, or MVIC. For both BFR-75 and BFR-4x, perceived muscle soreness increased (P<0.001) similarly 24- (2.5±1.7 AU) and 48-hours (1.9±1.7 AU) post-exercise. CONCLUSIONS: There was an increase in muscle soreness 24-48 hours post-exercise for both conditions, which may be due to metabolic stress, but this did not affect the force-generating capacity of the muscle (MVIC), suggesting minimal EIMD. The conflicting evidence of EIMD following LL+BFR may be related to differences in restriction time or overall exercise time.

6.
Artículo en Inglés | MEDLINE | ID: mdl-38850420

RESUMEN

INTRODUCTION: Soft tissue sarcomas are a group of malignancies that commonly occur in the extremities. As deep lesions may exist within the confines of the muscular fascia, we postulate that local recurrence rates are higher for superficial soft tissue sarcomas managed by the standard of care. MATERIALS AND METHODS: A retrospective review was performed on 90 patients who underwent surgical resection of soft tissue sarcomas of the extremity from 2007 to 2015. Patients with minimum 2-year follow-up and adequate operative, pathologic, and clinical outcomes data were included. RESULTS: Mean age was 54 ± 18 years with 49 (54.4%) patients being male. Lesions in 77.8% of cases were deep, and 22.2% were superficial to fascia. Following the index surgical resection, a total of 33 (36.7%) patients had positive margins. A total of 17 (18.9%) patients had a local recurrence. Overall, 3-year survival was 92.7%, and 5-year survival was 79.0%. Five-year recurrence-free survival of deep sarcomas was 91.1% versus 58.2% of superficial lesions (p = 0.006). Patients with higher tumor depth had lower odds of experiencing a local recurrence (HR 0.26 [95% CI 0.09-0.72]). Local recurence rates was also associated with positive surgical margins on initial resection (33.3% versus 12.3%) (p = 0.027). CONCLUSIONS: In this series, superficial tumor depth was associated with local recurrence of soft tissue sarcomas of the extremity following surgical resection. Positive surgical margins was also associated with local recurrence.

8.
Int J Mol Sci ; 25(11)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38892347

RESUMEN

V-set immunoglobulin domain-containing 4 (VSIG4) is a B7 family protein with known roles as a C3 fragment complement receptor involved in pathogen clearance and a negative regulator of T cell activation by an undetermined mechanism. VSIG4 expression is specific for tumor-associated and select tissue-resident macrophages. Increased expression of VSIG4 has been associated with worse survival in multiple cancer indications. Based upon computational analysis of transcript data across thousands of tumor and normal tissue samples, we hypothesized that VSIG4 has an important role in promoting M2-like immune suppressive macrophages and that targeting VSIG4 could relieve VSIG4-mediated macrophage suppression by repolarizing tumor-associated macrophages (TAMs) to an inflammatory phenotype. We have also observed a cancer-specific pattern of VSIG4 isoform distribution, implying a change in the functional regulation in cancer. Through a series of in vitro, in vivo, and ex vivo assays we demonstrate that anti-VSIG4 antibodies repolarize M2 macrophages and induce an immune response culminating in T cell activation. Anti-VSIG4 antibodies induce pro-inflammatory cytokines in M-CSF plus IL-10-driven human monocyte-derived M2c macrophages. Across patient-derived tumor samples from multiple tumor types, anti-VSIG4 treatment resulted in the upregulation of cytokines associated with TAM repolarization and T cell activation and chemokines involved in immune cell recruitment. VSIG4 blockade is also efficacious in a syngeneic mouse model as monotherapy as it enhances efficacy in combination with anti-PD-1, and the effect is dependent on the systemic availability of CD8+ T cells. Thus, VSIG4 represents a promising new target capable of triggering an anti-cancer response via multiple key immune mechanisms.


Asunto(s)
Neoplasias , Macrófagos Asociados a Tumores , Animales , Humanos , Ratones , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Neoplasias/inmunología , Neoplasias/metabolismo , Línea Celular Tumoral , Activación de Linfocitos/inmunología , Ratones Endogámicos C57BL , Citocinas/metabolismo , Femenino , Receptores de Complemento
9.
JAMA Netw Open ; 7(6): e2417440, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38884994

RESUMEN

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Anciano , Adulto , Síndrome Post Agudo de COVID-19 , Pandemias , Estados Unidos/epidemiología
10.
Int J Radiat Oncol Biol Phys ; 119(3): 719-720, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38851271
11.
Ann Emerg Med ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38878022

RESUMEN

STUDY OBJECTIVE: United States prescribing information recommends against coadministration of injectable olanzapine with injectable benzodiazepines due to a risk of cardiorespiratory depression, whereas European prescribing information recommends the 2 drugs not be administered within 60 minutes of each other. In contrast, a recently published American College of Emergency Physicians clinical policy recommends injectable olanzapine and benzodiazepines be coadministered for treating severe agitation. We sought to compare injectable olanzapine with and without injectable benzodiazepines for evidence of cardiorespiratory depression. METHODS: We performed a retrospective study of patients in an urban emergency department from January 2017 through November 2019 who received parenteral olanzapine with or without parenteral benzodiazepines. We included patients receiving 2 total medication doses, either olanzapine+benzodiazepine or 2 doses of olanzapine, coadministered within 60 minutes. The primary outcome was tracheal intubation in the emergency department. Secondary outcomes included hypotension (systolic blood pressure less than 90 mmHg) and hypoxemia (SpO2 less than 90%). RESULTS: We identified 693 patients (median [alcohol]=210 mg/dL, median age=37 years [IQR 29 to 49]). In total, 549 received 2 doses of olanzapine, and 144 patients received olanzapine and a benzodiazepine. We found no difference in intubation rates between the olanzapine-only group (21/549, 3.8%) and the olanzapine+benzodiazepine group (5/144, 3.5%; difference=0.3%, 95% confidence interval -3.0% to 3.7%). Rates of hypoxemia (2% olanzapine-only and 3% olanzapine+benzodiazepine) and hypotension (9% both groups) also were not different between groups. CONCLUSION: We found no difference in cardiorespiratory depression between patients receiving only olanzapine versus olanzapine plus a benzodiazepine.

12.
Matrix Biol Plus ; 23: 100153, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38882396

RESUMEN

Fish oils rank among the world's most popular nutritional supplements and are purported to have numerous health benefits. Previous work suggested that fish oils increase collagen production; however, the effect of fish oils on musculoskeletal health is poorly understood. Further, the divergent effects of omega-3 (Ω3FA) and saturated fatty acids (SFA) remains poorly understood. We tested the effects of Ω3FA and SFAs on in vitro-engineered human ligament (EHL) function. EHLs were treated with bovine serum albumin (BSA)-conjugated eicosapentaenoic acid (EPA, 20:5(n-3)), palmitic acid (PA, 16:0), or a BSA control for 6 days. EPA did not significantly alter, whereas PA significantly decreased EHL function and collagen content. To determine whether this was an in vitro artifact, mice were fed a control or high-lard diet for 14 weeks and musculoskeletal mass, insulin sensitivity, and the collagen content, and mechanics of tendon and bone were determined. Body weight was 40 % higher on a HFD, but muscle, tendon, and bone mass did not keep up with body weight resulting in relative losses in muscle mass, tendon, and bone collagen, as well as mechanical properties. Importantly, we show that PA acutely decreases collagen synthesis in vitro to a similar extent as the decrease in collagen content with chronic treatment. These data suggest that Ω3FAs have a limited effect on EHLs, whereas SFA exert a negative effect on collagen synthesis resulting in smaller and weaker musculoskeletal tissues both in vitro and in vivo.

13.
Neurosurgery ; 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38842298

RESUMEN

BACKGROUND AND OBJECTIVES: The treatment of brain arteriovenous malformations (AVMs) involves multiple approaches, including embolization, microsurgical resection, and radiosurgery. With the advent of new embolisates, dual-lumen balloon catheters, detachable tip microcatheters, and transvenous embolization, endovascular AVM obliteration has become more effective. Although adjuvant embolization and embolization are commonly used, the safety and effectiveness of curative embolization remain unclear. METHODS: We conducted a systematic literature review using PubMed, Ovid Medline, and Web of Science to identify studies reporting outcomes in patients with AVMs who underwent primary embolization with the intention to cure. We collected data on patient characteristics, AVM features, complications, and radiographic and clinical outcomes for meta-analysis. RESULTS: We identified 25 studies with a total of 1425 patients with 1427 AVMs who underwent curative embolization. Of these patients, 70% were low grade (pooled = 61% [39-82]), 67% were <3 cm (pooled = 78% [60-92]), and 75% were in superficial locations (pooled = 80% [72-86]). At last radiographic follow-up (mean, 16.7 ± 10.9 months), the full obliteration rate was 52% (pooled = 61% [43-77]) and retreatment rate was 25% (pooled = 17% [8.3-27]). At last clinical follow-up (mean, 24.2 ± 13.3 months), the poor clinical outcome rate was 7.9% (pooled = 4.4% [1.3-8.7]) and symptomatic complication rate was 13% (pooled = 13% [8-19]). There was no significant difference in the rate of radiographic cure, need for retreatment, and poor outcomes between ruptured and unruptured AVMs. Symptomatic complications were more common in the treatment of unruptured AVMs. The primary outcomes showed high heterogeneity (I2 = 72%-94%). CONCLUSION: Curative embolization of AVM is primarily reserved for small and low-grade AVMs, with highly variable outcomes. Our findings suggest poor radiographic outcomes and increased risk of complications. Outcomes are highly dependent on patient selection and technique used. Large multicenter prospective studies are required to further guide patient selection, categorize clinical and radiographic outcomes, and identify subgroup of patients that may benefit from curative embolization.

14.
Bioinformatics ; 40(6)2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38796681

RESUMEN

MOTIVATION: Post-translational modifications (PTMs) on proteins regulate protein structures and functions. A single protein molecule can possess multiple modification sites that can accommodate various PTM types, leading to a variety of different patterns, or combinations of PTMs, on that protein. Different PTM patterns can give rise to distinct biological functions. To facilitate the study of multiple PTMs on the same protein molecule, top-down mass spectrometry (MS) has proven to be a useful tool to measure the mass of intact proteins, thereby enabling even PTMs at distant sites to be assigned to the same protein molecule and allowing determination of how many PTMs are attached to a single protein. RESULTS: We developed a Python module called MSModDetector that studies PTM patterns from individual ion mass spectrometry (I2MS) data. I2MS is an intact protein mass spectrometry approach that generates true mass spectra without the need to infer charge states. The algorithm first detects and quantifies mass shifts for a protein of interest and subsequently infers potential PTM patterns using linear programming. The algorithm is evaluated on simulated I2MS data and experimental I2MS data for the tumor suppressor protein p53. We show that MSModDetector is a useful tool for comparing a protein's PTM pattern landscape across different conditions. An improved analysis of PTM patterns will enable a deeper understanding of PTM-regulated cellular processes. AVAILABILITY AND IMPLEMENTATION: The source code is available at https://github.com/marjanfaizi/MSModDetector.


Asunto(s)
Algoritmos , Espectrometría de Masas , Procesamiento Proteico-Postraduccional , Programas Informáticos , Espectrometría de Masas/métodos , Proteína p53 Supresora de Tumor/metabolismo , Bases de Datos de Proteínas , Proteínas/metabolismo , Proteínas/química
15.
Prehosp Emerg Care ; : 1-5, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38781490

RESUMEN

Sodium nitrite overdose leads to profound methemoglobinemia and may quickly progress to death. It is an increasingly common method of suicide and is often fatal. Methylene blue is an effective but time-sensitive antidote that has the potential to save lives when administered early. In this case report, we describe a fatal sodium nitrite overdose and the subsequent creation of a prehospital protocol for our large urban Emergency Medical Services system.

16.
J Prim Care Community Health ; 15: 21501319241254751, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808863

RESUMEN

BACKGROUND: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1ß, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs. METHODS: The clinical cytokine panel was analyzed in patients with Long COVID during periods that were stratified according to variant epoch. The 4 variant epochs were defined as: (1) wild-type through alpha, (2) alpha/beta/gamma, (3) delta, and (4) omicron variants. RESULTS: A total of 390 patients had the clinical cytokine panel performed; the median age was 48 years (IQR 38-59) and 62% were female. Distribution by variant was wild-type and alpha, 50% (n = 196); alpha/beta/gamma, 7.9% (n = 31); delta, 18% (n = 72); and omicron, 23% (n = 91). Time to cytokine panel testing was significantly longer for the earlier epochs. Tumor necrosis factor-α (P < .001) and interleukin 1ß (P < .001) were significantly more elevated in the earlier epochs (median of 558 days in wild-type through Alpha epoch vs 263 days in omicron epoch, P < .001)). Nucleocapsid antibodies were consistently detected across epochs. DISCUSSION: When stratified by variant epoch, patients with early epoch Long COVID had persistently elevated peripheral pro-inflammatory cytokine levels when compared to later epoch Long COVID. Patients with Long COVID have similar clusters of symptoms across epochs, suggesting that the underlying pathology is independent of the peripheral cytokine signature.


Asunto(s)
COVID-19 , Citocinas , SARS-CoV-2 , Humanos , Femenino , Persona de Mediana Edad , Masculino , Citocinas/sangre , COVID-19/inmunología , COVID-19/sangre , Adulto , SARS-CoV-2/inmunología , Síndrome Post Agudo de COVID-19 , Interleucina-1beta/sangre , Factor de Necrosis Tumoral alfa/sangre , Interleucina-6/sangre
17.
APL Bioeng ; 8(2): 026106, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38715647

RESUMEN

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a routine method to noninvasively quantify perfusion dynamics in tissues. The standard practice for analyzing DCE-MRI data is to fit an ordinary differential equation to each voxel. Recent advances in data science provide an opportunity to move beyond existing methods to obtain more accurate measurements of fluid properties. Here, we developed a localized convolutional function regression that enables simultaneous measurement of interstitial fluid velocity, diffusion, and perfusion in 3D. We validated the method computationally and experimentally, demonstrating accurate measurement of fluid dynamics in situ and in vivo. Applying the method to human MRIs, we observed tissue-specific differences in fluid dynamics, with an increased fluid velocity in breast cancer as compared to brain cancer. Overall, our method represents an improved strategy for studying interstitial flows and interstitial transport in tumors and patients. We expect that our method will contribute to the better understanding of cancer progression and therapeutic response.

19.
Elife ; 132024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739430

RESUMEN

A comprehensive census of McrBC systems, among the most common forms of prokaryotic Type IV restriction systems, followed by phylogenetic analysis, reveals their enormous abundance in diverse prokaryotes and a plethora of genomic associations. We focus on a previously uncharacterized branch, which we denote coiled-coil nuclease tandems (CoCoNuTs) for their salient features: the presence of extensive coiled-coil structures and tandem nucleases. The CoCoNuTs alone show extraordinary variety, with three distinct types and multiple subtypes. All CoCoNuTs contain domains predicted to interact with translation system components, such as OB-folds resembling the SmpB protein that binds bacterial transfer-messenger RNA (tmRNA), YTH-like domains that might recognize methylated tmRNA, tRNA, or rRNA, and RNA-binding Hsp70 chaperone homologs, along with RNases, such as HEPN domains, all suggesting that the CoCoNuTs target RNA. Many CoCoNuTs might additionally target DNA, via McrC nuclease homologs. Additional restriction systems, such as Type I RM, BREX, and Druantia Type III, are frequently encoded in the same predicted superoperons. In many of these superoperons, CoCoNuTs are likely regulated by cyclic nucleotides, possibly, RNA fragments with cyclic termini, that bind associated CARF (CRISPR-Associated Rossmann Fold) domains. We hypothesize that the CoCoNuTs, together with the ancillary restriction factors, employ an echeloned defense strategy analogous to that of Type III CRISPR-Cas systems, in which an immune response eliminating virus DNA and/or RNA is launched first, but then, if it fails, an abortive infection response leading to PCD/dormancy via host RNA cleavage takes over.


All organisms, from animals to bacteria, are subject to genetic parasites, such as viruses and transposons. Genetic parasites are pieces of nucleic acids (DNA or RNA) that can use a cell's machinery to copy themselves at the expense of their hosts. This often leads to the host's demise, so organisms evolved many types of defense mechanisms. One of the most ancient and common forms of defense against viruses and transposons is the targeted restriction of nucleic acids, that is, deployment of host enzymes that can destroy or restrict nucleic acids containing specific sequence motifs or modifications. In bacteria, many of the restriction enzymes targeting parasitic genetic elements are formed by fusions of proteins from the so-called McrBC systems with a protein domain called EVE. EVE and other functionally similar domains are a part of proteins that recognize and bind modified bases in nucleic acids. Enzymes can use the ability of these specificity domains to bind modified bases to detect non-host nucleic acids. Bell et al. conducted a comprehensive computational search for McrBC systems and discovered a large and highly diverse branch of this family with unusual characteristic structural and functional domains. These features include regions that form long alpha-helices (coils) that coil with other alpha-helices (known as coiled-coils), as well as several distinct enzymatic domains that break down nucleic acids (known as nucleases). They call these systems CoCoNuTs (coiled-coiled nuclease tandems). All CoCoNuTs contain domains, including EVE-like ones, which are predicted to interact with components of the RNA-based systems responsible for producing proteins in the cell (translation), suggesting that the CoCoNuTs have an important impact on protein abundance and RNA metabolism. Bell et al.'s findings will be of interest to scientists working on prokaryotic immunity and virulence. Furthermore, similarities between CoCoNuTs and components of eukaryotic RNA-degrading systems suggest evolutionary connections between this diverse family of bacterial predicted RNA restriction systems and RNA regulatory pathways of eukaryotes. Further deciphering the mechanisms of CoCoNuTs could shed light on how certain pathways of RNA metabolism and regulation evolved, and how they may contribute to advances in biotechnology.


Asunto(s)
ARN Bacteriano , ARN Bacteriano/metabolismo , ARN Bacteriano/química , ARN Bacteriano/genética , Filogenia , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Bacterias/genética , Bacterias/metabolismo , ARN/metabolismo , ARN/genética , ARN/química
20.
Curr Nutr Rep ; 13(2): 323-330, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38696073

RESUMEN

PURPOSE OF REVIEW: Securing safe and effective intravenous (IV) access is of utmost importance for administering parenteral nutrition (PN). Sustaining this access can indeed pose challenges, especially when dealing with the risk of complications associated with long-term PN. This review emphasizes best practices to optimize intravenous access and reviews the current evidence-based recommendations and consensus guidelines. RECENT FINDINGS: An individualized approach when selecting central venous catheters (CVC) is recommended, considering the estimated duration of need for IV access and the number of lumens needed. Established and novel approaches to minimize complications, including infection and thrombosis, are recognized. These include placement and positioning of the catheter tip under sonographic guidance and the use of antimicrobial lock therapies. Moreover, when possible, salvaging CVCs can reduce the risk of vascular access loss. CVC selection for patients requiring PN depends on several factors. Carefully reviewing an individual patient's clinical characteristics and discussing options is important. Given the increased infection risk, CVC lumens should be minimized. For long-term PN beyond 6 months, using CVCs with skin barriers and larger diameters should be considered.


Asunto(s)
Cateterismo Venoso Central , Catéteres Venosos Centrales , Nutrición Parenteral , Humanos , Cateterismo Venoso Central/efectos adversos , Infecciones Relacionadas con Catéteres/prevención & control , Guías de Práctica Clínica como Asunto
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