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1.
Free Radic Biol Med ; 223: 341-356, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39147070

RESUMEN

The mechanisms leading to a predominantly hypertrophied phenotype versus a predominantly oxidative phenotype, the hallmarks of resistance training (RT) or aerobic training (AT), respectively, are being unraveled. In humans, exposure of naïve persons to either AT or RT results in their skeletal muscle exhibiting generic 'exercise stress-related' signaling, transcription, and translation responses. However, with increasing engagement in AT or RT, the responses become refined, and the phenotype typically associated with each form of exercise emerges. Here, we review some of the mechanisms underpinning the adaptations of how muscles become, through AT, 'fit' and RT, 'mighty.' Much of our understanding of molecular exercise physiology has arisen from targeted analysis of post-translational modifications and measures of protein synthesis. Phosphorylation of specific residue sites has been a dominant focus, with canonical signaling pathways (AMPK and mTOR) studied extensively in the context of AT and RT, respectively. These alone, along with protein synthesis, have only begun to elucidate key differences in AT and RT signaling. Still, key yet uncharacterized differences exist in signaling and regulation of protein synthesis that drive unique adaptation to AT and RT. Omic studies are required to better understand the divergent relationship between exercise and phenotypic outcomes of training.


Asunto(s)
Adaptación Fisiológica , Ejercicio Físico , Músculo Esquelético , Entrenamiento de Fuerza , Transducción de Señal , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Ejercicio Físico/fisiología , Procesamiento Proteico-Postraduccional , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Fosforilación
2.
Am Surg ; 90(6): 1570-1576, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38592191

RESUMEN

BACKGROUND: There lacks rapid standardized bedside testing to screen cognitive deficits following mild traumatic brain injury (mTBI). Immediate Post-Concussion Assessment & Cognitive Testing-Quick Test (ImPACT-QT) is an abbreviated-iPad form of computerized cognitive testing. The aim of this study is to test ImPACT-QT utility in inpatient settings. We hypothesize ImPACT-QT is feasible in the acute trauma setting. METHOD: Trauma patients ages 12-70 were administered ImPACT-QT (09/2022-09/2023). Encephalopathic/medically unstable patients were excluded. Mild traumatic brain injury was defined as documented-head trauma with loss-of-consciousness <30 minutes and arrival Glasgow Coma Scale 13-15. Patients answered Likert-scale surveys. Bivariate analyses compared demographics, attention, motor speed, and memory scores between mTBI and non-TBI controls. Multivariable logistic regression assessed memory score as a predictor of mTBI diagnosis. RESULTS: Of 233 patients evaluated (36 years [IQR 23-50], 71% [166/233] female), 179 (76%) were mTBI patients. For all patients, mean test-time was 9.3 ± 2 minutes with 93% (73/76) finding the test "easy to understand." Mild traumatic brain injury patients than non-TBI control had lower memory scores (25 [IQR 7-100] vs 43 [26-100], P = .001) while attention (5 [1-23] vs 11 [1-32]) and motor score (14 [3-28] vs 13 [4-32]) showed no significant differences. Multivariable-regression (adjustment: age, sex, race, education level, ISS, and time to test) demonstrated memory score predicted mTBI positive status (OR .96, CI .94-.98, P = .004). DISCUSSION: Immediate Post-Concussion Assessment & Cognitive Testing-Quick Test is feasible in trauma patients. Preliminary findings suggest acute mTBIs have lower memory but not attention/motor scores vs non-TBI trauma controls.


Asunto(s)
Conmoción Encefálica , Pruebas Neuropsicológicas , Centros Traumatológicos , Humanos , Femenino , Masculino , Adulto , Conmoción Encefálica/diagnóstico , Conmoción Encefálica/complicaciones , Persona de Mediana Edad , Adolescente , Adulto Joven , Computadoras de Mano , Anciano , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Niño , Pruebas en el Punto de Atención , Escala de Coma de Glasgow
3.
J Virol ; 98(4): e0013224, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38511932

RESUMEN

Heartland virus (HRTV) is an emerging tick-borne bandavirus that causes a febrile illness of varying severity in humans, with cases reported in eastern and midwestern regions of the United States. No vaccines or approved therapies are available to prevent or treat HRTV disease. Here, we describe the genetic changes, natural history of disease, and pathogenesis of a mouse-adapted HRTV (MA-HRTV) that is uniformly lethal in 7- to 8-week-old AG129 mice at low challenge doses. We used this model to assess the efficacy of the ribonucleoside analog, 4'-fluorouridine (EIDD-2749), and showed that once-daily oral treatment with 3 mg/kg of drug, initiated after the onset of disease, protects mice against lethal MA-HRTV challenge and reduces viral loads in blood and tissues. Our findings provide insights into HRTV virulence and pathogenesis and support further development of EIDD-2749 as a therapeutic intervention for HRTV disease. IMPORTANCE: More than 60 cases of HRTV disease spanning 14 states have been reported to the United States Centers for Disease Control and Prevention. The expanding range of the Lone Star tick that transmits HRTV, the growing population of at-risk persons living in geographic areas where the tick is abundant, and the lack of antiviral treatments or vaccines raise significant public health concerns. Here, we report the development of a new small-animal model of lethal HRTV disease to gain insight into HRTV pathogenesis and the application of this model for the preclinical development of a promising new antiviral drug candidate, EIDD-2749. Our findings shed light on how the virus causes disease and support the continued development of EIDD-2749 as a therapeutic for severe cases of HRTV infection.


Asunto(s)
Infecciones por Bunyaviridae , Bunyaviridae , Nucleótidos de Uracilo , Animales , Humanos , Ratones , Infecciones por Bunyaviridae/tratamiento farmacológico , Garrapatas , Estados Unidos , Nucleótidos de Uracilo/uso terapéutico
4.
J Virol ; 98(4): e0011224, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38506509

RESUMEN

Live-attenuated virus vaccines provide long-lived protection against viral disease but carry inherent risks of residual pathogenicity and genetic reversion. The live-attenuated Candid#1 vaccine was developed to protect Argentines against lethal infection by the Argentine hemorrhagic fever arenavirus, Junín virus. Despite its safety and efficacy in Phase III clinical study, the vaccine is not licensed in the US, in part due to concerns regarding the genetic stability of attenuation. Previous studies had identified a single F427I mutation in the transmembrane domain of the Candid#1 envelope glycoprotein GPC as the key determinant of attenuation, as well as the propensity of this mutation to revert upon passage in cell culture and neonatal mice. To ascertain the consequences of this reversion event, we introduced the I427F mutation into recombinant Candid#1 (I427F rCan) and investigated the effects in two validated small-animal models: in mice expressing the essential virus receptor (human transferrin receptor 1; huTfR1) and in the conventional guinea pig model. We report that I427F rCan displays only modest virulence in huTfR1 mice and appears attenuated in guinea pigs. Reversion at another attenuating locus in Candid#1 GPC (T168A) was also examined, and a similar pattern was observed. By contrast, virus bearing both revertant mutations (A168T+I427F rCan) approached the lethal virulence of the pathogenic Romero strain in huTfR1 mice. Virulence was less extreme in guinea pigs. Our findings suggest that genetic stabilization at both positions is required to minimize the likelihood of reversion to virulence in a second-generation Candid#1 vaccine.IMPORTANCELive-attenuated virus vaccines, such as measles/mumps/rubella and oral poliovirus, provide robust protection against disease but carry with them the risk of genetic reversion to the virulent form. Here, we analyze the genetics of reversion in the live-attenuated Candid#1 vaccine that is used to protect against Argentine hemorrhagic fever, an often-lethal disease caused by the Junín arenavirus. In two validated small-animal models, we find that restoration of virulence in recombinant Candid#1 viruses requires back-mutation at two positions specific to the Candid#1 envelope glycoprotein GPC, at positions 168 and 427. Viruses bearing only a single change showed only modest virulence. We discuss strategies to genetically harden Candid#1 GPC against these two reversion events in order to develop a safer second-generation Candid#1 vaccine virus.


Asunto(s)
Fiebre Hemorrágica Americana , Virus Junin , Vacunas Virales , Animales , Cobayas , Humanos , Ratones , Glicoproteínas/genética , Fiebre Hemorrágica Americana/prevención & control , Virus Junin/fisiología , Pueblos Sudamericanos , Vacunas Atenuadas/genética , Vacunas Virales/genética , Virulencia
5.
Orphanet J Rare Dis ; 19(1): 67, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38360726

RESUMEN

INTRODUCTION: Ataxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets of individuals with A-T beyond mild and classic phenotypes, enabling identification of novel features for disease classification and treatment response to therapy. METHODS: Participants with classic A-T (n = 77), mild A-T (n = 13), and unaffected controls (n = 15) were recruited from two outpatient clinics. PBMCs were isolated and bulk RNAseq was performed. Plasma was also isolated in a subset of individuals. Affected individuals were designated mild or classic based on ATM mutations and clinical and laboratory features. RESULTS: People with classic A-T were more likely to be younger and IgA deficient and to have higher alpha-fetoprotein levels and lower % forced vital capacity compared to individuals with mild A-T. In classic A-T, the expression of genes required for V(D)J recombination was lower, and the expression of genes required for inflammatory activity was higher. We assigned inflammatory scores to study participants and found that inflammatory scores were highly variable among people with classic A-T and that higher scores were associated with lower ATM mRNA levels. Using a cell type deconvolution approach, we inferred that CD4 + T cells and CD8 + T cells were lower in number in people with classic A-T. Finally, we showed that individuals with classic A-T exhibit higher SERPINE1 (PAI-1) mRNA and plasma protein levels, irrespective of age, and higher FLT4 (VEGFR3) and IL6ST (GP130) plasma protein levels compared with mild A-T and controls. CONCLUSION: Using a transcriptomic approach, we identified novel features and developed an inflammatory score to identify subsets of individuals with different inflammatory phenotypes in A-T. Findings from this study could be used to help direct treatment and to track treatment response to therapy.


Asunto(s)
Ataxia Telangiectasia , Enfermedades Neurodegenerativas , Humanos , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/metabolismo , Leucocitos Mononucleares/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Fenotipo , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , ARN Mensajero/metabolismo
6.
J Cell Physiol ; 239(4): e31182, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38214457

RESUMEN

Ribosomes are essential cellular machinery for protein synthesis. It is hypothesised that ribosome content supports muscle growth and that individuals with more ribosomes have greater increases in muscle size following resistance training (RT). Aerobic conditioning (AC) also elicits distinct physiological adaptations; however, no measures of ribosome content following AC have been conducted. We used ribosome-related gene expression as a proxy measure for ribosome content and hypothesised that AC and RT would increase ribosome-related gene expression. Fourteen young men and women performed 6 weeks of single-legged AC followed by 10 weeks of double-legged RT. Muscle biopsies were taken following AC and following RT in the aerobically conditioned (AC+RT) and unconditioned (RT) legs. No differences in regulatory genes (Ubf, Cyclin D1, Tif-1a and Polr-1b) involved in ribosomal biogenesis or ribosomal RNA (45S, 5.8S, 18S and 28S rRNAs) expression were observed following AC and RT, except for c-Myc (RT > AC+RT) and 5S rRNA (RT < AC+RT at pre-RT) with 18S external transcribed spacer and 5.8S internal transcribed spacer expression decreasing from pre-RT to post-RT in the RT leg only. When divided for change in leg-lean soft tissue mass (ΔLLSTM) following RT, legs with the greatest ΔLLSTM had lower expression in 11/13 measured ribosome-related genes before RT and decreased expression in 9/13 genes following RT. These results indicate that AC and RT did not increase ribosome-related gene expression. Contrary to previous research, the greatest increase in muscle mass was associated with lower changes in ribosome-related gene expression over the course of the 10-week training programme. This may point to the importance of translational efficiency rather than translational capacity (i.e. ribosome content) in mediating long-term exercise-induced adaptations in skeletal muscle.


Asunto(s)
Músculo Esquelético , Entrenamiento de Fuerza , Ribosomas , Femenino , Humanos , Masculino , Regulación de la Expresión Génica , Hipertrofia/genética , Hipertrofia/metabolismo , Músculo Esquelético/metabolismo , Biosíntesis de Proteínas/genética , Ribosomas/genética , Adulto Joven
7.
J Pers Med ; 14(1)2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38248767

RESUMEN

While congenital heart disease historically was a pathology primarily restricted to specialized pediatric centers, advances in technology have dramatically increased the number of people living into adulthood, the number of complications faced by these patients, and the number of patients visiting non-specialized emergency departments for these concerns. Clinicians need to be aware of the issues specific to patients' individual congenital defects but also have an understanding of how typical cardiac pathology may manifest in this special group of patients. This manuscript attempts to provide an overview of this diverse but increasingly common group of adult patients with congenital heart diseases, including a review of their anatomical variants, the complications they face at the highest rates, and ways that emergency physicians may need to manage these patients differently to avoid causing harm.

8.
Sports Biomech ; : 1-16, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38193478

RESUMEN

The aim of this study was to examine spatiotemporal and joint kinematic differences between footstrike patterns in 10,000 m running. Seventy-two men's and 42 women's footstrike patterns were analysed during laps 5, 10, 15, 20 and 25 (of 25) using 2D video recordings. Approximately 47% of men were FFS throughout the race, 30% were MFS and 24% RFS; the respective frequencies in women were approximately 30%, 38% and 32%. Overall, 83% of men and 88% of women retained their footstrike pattern throughout the race. Amongst the 53 men and 33 women with symmetrical footstrike patterns, there were no differences in speed, step length or cadence between footstrike groups in either sex. Most lower limb joint angles did not change in these athletes during the event, with few differences between footstrike patterns apart from ankle and foot angles. A greater hip-ankle distance was found in RFS than in FFS (both sexes) and in RFS than in MFS (men only), although these differences were never more than 0.03 m. Coaches should note that habitual footstrike patterns were maintained during this long-distance track race despite changes in running speed and possible fatigue, and there were few performance differences between footstrike patterns.

9.
Med Teach ; : 1-8, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38295768

RESUMEN

BACKGROUND: Scottish Graduate Entry Medicine (ScotGEM) is a new four-year graduate entry medical programme. During the third year, students undertake a Longitudinal Integrated Clerkship (LIC) where they are integrated into one General Practice for two and a half days a week. The remaining time is 'white space', allowing students to undertake placements and portfolio work; while directing their learning. AIMS: To explore the students' perceptions of the utility of the 'white space' of the ScotGEM LIC. Secondary aims were to explore the positive aspects of this space, the challenges of utilising this space and to explore any difference in the 'white space' between LIC regions. METHODS: An explorative case study methodology was utilised and semi-structured interviews were conducted with third and fourth-year students. 13 interviews were transcribed for inductive thematic analysis. FINDINGS: Four themes were established: the students' usage of the 'white space'; the tools they used to guide learning in this space; regional variations in LIC experiences and they offered suggestions to improve the utility of this space. DISCUSSION AND CONCLUSION: The findings are detailed and integrated with relevant literature to inform recommendations for future LIC practice and suggestions for future research are offered.

10.
Gait Posture ; 108: 208-214, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38118224

RESUMEN

BACKGROUND: Controlled ankle motion (CAM) boots are often prescribed during the rehabilitation of lower limb injuries and pathologies to reduce foot and ankle movement and loading whilst allowing the patient to maintain normal daily function. RESEARCH QUESTION: The aim of this study was to quantify the compensatory biomechanical mechanisms undergone by the ipsilateral hip and knee joints during walking. In addition, the compensatory mechanisms displayed by the contralateral limb were also considered. METHODS: Twelve healthy participants walked on an instrumented treadmill at their preferred walking speed. They underwent kinematic and kinetic analysis during four footwear conditions: normal shoes (NORM), a Malleo Immobil Air Walker on the right leg (OTTO), a Rebound® Air Walker on the right leg with (EVEN) and without (OSS) an Evenup Shoelift™ on the contralateral leg. RESULTS: CAM boot wear increased the relative joint contribution to total mechanical work from the ipsilateral hip and knee joints (p < 0.05), which was characterised by increased hip and knee abduction during the swing phase of the gait cycle. EVEN increased the absolute work done and relative contribution of the contralateral limb. CAM boot wear reduced walking speed (p < 0.05), which was partially compensated for during EVEN. SIGNIFICANCE: The increased hip abduction in the ipsilateral leg was likely caused by the increase in effective leg length and limb mass, which could lead to secondary site complications following prolonged CAM boot wear. Although prescribing an even-up walker partially mitigates these compensatory mechanisms, adverse effects to contralateral limb kinematics and kinetics (e.g., elevated knee joint work) should be considered.


Asunto(s)
Tobillo , Caminata , Humanos , Cinética , Caminata/fisiología , Marcha/fisiología , Extremidad Inferior , Articulación del Tobillo/fisiología , Articulación de la Rodilla , Fenómenos Biomecánicos
11.
Sensors (Basel) ; 23(23)2023 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-38067758

RESUMEN

Traffic flow analysis is essential to develop smart urban mobility solutions. Although numerous tools have been proposed, they employ only a small number of parameters. To overcome this limitation, an edge computing solution is proposed based on nine traffic parameters, namely, vehicle count, direction, speed, and type, flow, peak hour factor, density, time headway, and distance headway. The proposed low-cost solution is easy to deploy and maintain. The sensor node is comprised of a Raspberry Pi 4, Pi camera, Intel Movidius Neural Compute Stick 2, Xiaomi MI Power Bank, and Zong 4G Bolt+. Pre-trained models from the OpenVINO Toolkit are employed for vehicle detection and classification, and a centroid tracking algorithm is used to estimate vehicle speed. The measured traffic parameters are transmitted to the ThingSpeak cloud platform via 4G. The proposed solution was field-tested for one week (7 h/day), with approximately 10,000 vehicles per day. The count, classification, and speed accuracies obtained were 79.8%, 93.2%, and 82.9%, respectively. The sensor node can operate for approximately 8 h with a 10,000 mAh power bank and the required data bandwidth is 1.5 MB/h. The proposed edge computing solution overcomes the limitations of existing traffic monitoring systems and can work in hostile environments.

12.
Vet Immunol Immunopathol ; 265: 110677, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37952345

RESUMEN

Bovine Johne's disease (BJD) or paratuberculosis is caused by Mycobacterium avium spp. paratuberculosis (MAP) and is a worldwide problem among domestic and wild ruminants. While vaccines are available, natural differences in background immunity between breeds within species and between individuals within herds suggest that genetic differences may be able to be exploited in marker-assisted selection as an aid to disease control. The major histocompatibility complex (MHC) is an important component in immune recognition with considerable genetic variability. In this study, associations between the MHC and resistance to BJD were explored in dairy cattle across two herds in which some of the cattle had been vaccinated with Silirum® (n = 540 cows). A BJD susceptible animal was exposed to MAP and became infected, while a resistant animal was exposed but did not become infected. There are different ways to define both exposure and infection, with different levels of stringency, therefore many classifications of the same set of animals are possible and were included in the analysis. The polymorphic regions of major histocompatibility complex class I (MHC I) and class II (MHC II) genes were amplified from the genomic DNA by PCR and sequenced, targeting exons 2 and 3 of the classical and non-classical MHC I genes and exon 2 from the DRB3, DQA1, DQA2 + 3 and DQB MHC II genes. The frequencies of MHC I and MHC II haplotypes and alleles were determined in susceptible and resistant populations. In unvaccinated animals, seven MHC I haplotypes and seven MHC II haplotypes were associated with susceptibility while two MHC I and six MHC II haplotypes were associated with resistance (P < 0.05). In vaccinated animals, two MHC I and three MHC II haplotypes were associated with susceptibility, while one MHC I and two MHC II haplotypes were associated with resistance (P < 0.05). The alleles in significant haplotypes were also identified. Case definitions with higher stringency resulted in fewer animals being included in the analyses, but the power to detect an association was not reduced and there was an increase in strength and consistency of associations. Consistent use of stringent case definitions is likely to improve agreement in future association studies.


Asunto(s)
Enfermedades de los Bovinos , Paratuberculosis , Humanos , Femenino , Bovinos , Animales , Paratuberculosis/genética , Paratuberculosis/prevención & control , Haplotipos , Enfermedades de los Bovinos/genética , Enfermedades de los Bovinos/prevención & control , Susceptibilidad a Enfermedades/veterinaria , Complejo Mayor de Histocompatibilidad/genética
13.
MethodsX ; 11: 102366, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37767157

RESUMEN

Quantum field theory (QFTh) simulators simulate physical systems using quantum circuits that process quantum information (qubits) via single field (SF) and/or quantum double field (QDF) transformation. This review presents models that classify states against pairwise particle states |ij〉, given their state transition (ST) probability P|ij〉. A quantum AI (QAI) program, weighs and compares the field's distance between entangled states as qubits from their scalar field of radius R≥|rij|. These states distribute across 〈R〉 with expected probability 〈Pdistribute〉 and measurement outcome 〈M(Pdistribute)〉=P|ij〉. A quantum-classical hybrid model of processors via QAI, classifies and predicts states by decoding qubits into classical bits. For example, a QDF as a quantum field computation model (QFCM) in IBM-QE, performs the doubling of P|ij〉 for a strong state prediction outcome. QFCMs are compared to achieve a universal QFCM (UQFCM). This model is novel in making strong event predictions by simulating systems on any scale using QAI. Its expected measurement fidelity is 〈M(F)〉≥7/5 in classifying states to select 7 optimal QFCMs to predict 〈M〉's on QFTh observables. This includes QFCMs' commonality of 〈M〉 against QFCMs limitations in predicting system events. Common measurement results of QFCMs include their expected success probability 〈Psuccess〉 over STs occurring in the system. Consistent results with high F's, are averaged over STs as 〈Pdistribute〉yielding 〈Psuccess〉≥2/3 performed by an SF or QDF of certain QFCMs. A combination of QFCMs with this fidelity level predicts error rates (uncertainties) in measurements, by which a P|ij〉=〈Psuccess〉<∼1 is weighed as a QAI output to a QFCM user. The user then decides which QFCMs perform a more efficient system simulation as a reliable solution. A UQFCM is useful in predicting system states by preserving and recovering information for intelligent decision support systems in applied, physical, legal and decision sciences, including industry 4.0 systems.

14.
Cureus ; 15(8): e43638, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37719484

RESUMEN

Introduction Musculoskeletal (MSK) complaints and injuries account for a large percentage of presenting chief complaints to the emergency department in the United States (US). Despite the prevalence and economic impact on the US healthcare system, there is a documented deficiency in MSK education at all training and practicing levels in the US medical system. The purpose of this needs assessment is to better determine the state of MSK education in Emergency Medicine residency programs. Methods An online needs assessment form was sent to Emergency Medicine program directors in the US. Summary statistics were performed followed by an exploratory analysis. Results Data from 43 of 272 Emergency Medicine program directors that responded to this needs assessment were analyzed. Respondents ranked the importance of MSK education in Emergency Medicine on a Likert scale of 1-5 (very unimportant to very important) at a mean of 4.2. Additionally, 97.6% of respondents believe that their MSK curriculum could be improved. Seventy-nine percent of respondents were somewhat likely or highly likely to use a standardized method or tool to assess MSK knowledge. Of the top three barriers to MSK education implementation, 94.9% cited time, 56.4% cited interdepartmental relations, and 46.2% cited funding. Conclusion MSK knowledge is taught and assessed in highly variable methods across Emergency Medicine residency programs. Although efforts are being made to address the known deficiency in MSK knowledge, further research is needed to perform a larger needs assessment, study innovative MSK education modalities, and develop a standardized MSK assessment for Emergency Medicine residency training.

15.
Nucleic Acids Res ; 51(15): 8115-8132, 2023 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-37395408

RESUMEN

CRISPR-associated DinG protein (CasDinG) is essential to type IV-A CRISPR function. Here, we demonstrate that CasDinG from Pseudomonas aeruginosa strain 83 is an ATP-dependent 5'-3' DNA translocase that unwinds double-stranded (ds)DNA and RNA/DNA hybrids. The crystal structure of CasDinG reveals a superfamily 2 helicase core of two RecA-like domains with three accessory domains (N-terminal, arch, and vestigial FeS). To examine the in vivo function of these domains, we identified the preferred PAM sequence for the type IV-A system (5'-GNAWN-3' on the 5'-side of the target) with a plasmid library and performed plasmid clearance assays with domain deletion mutants. Plasmid clearance assays demonstrated that all three domains are essential for type IV-A immunity. Protein expression and biochemical assays suggested the vFeS domain is needed for protein stability and the arch for helicase activity. However, deletion of the N-terminal domain did not impair ATPase, ssDNA binding, or helicase activities, indicating a role distinct from canonical helicase activities that structure prediction tools suggest involves interaction with dsDNA. This work demonstrates CasDinG helicase activity is essential for type IV-A CRISPR immunity as well as the yet undetermined activity of the CasDinG N-terminal domain.


Asunto(s)
Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , ADN de Cadena Simple , ADN de Cadena Simple/genética , ADN Helicasas/metabolismo , ADN/genética , ARN Helicasas/genética , ARN
16.
Br J Oral Maxillofac Surg ; 61(4): 267-273, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37019738

RESUMEN

The maxillary artery (MA) is a key structure at risk of injury in numerous oral and maxillofacial surgical (OMS) procedures. Knowledge of safe distances from this vessel to surgically familiar bony landmarks could improve patient safety and prevent catastrophic haemorrhage. Distances between the MA and bony landmarks on the maxilla and mandible were measured using CT angiograms on 100 patients (200 facial halves). The vertical height of the pterygomaxillary junction (PMJ) was mean (SD) measurement of 16 (3) mm. The MA enters the pterygomaxillary fissure (PMF) a mean (SD) distance of 29 (3) mm from the most inferior point of the PMJ. The mean (SD) shortest distance between the MA and medial surface of the mandible was 2 (2) mm (with the vessel directly contacting the mandible in 17% of cases). The branchpoint (bifurcation of the superficial temporal artery (STA) and MA) was directly in contact with the mandible in 5% of cases. The mean (SD) distances between this bifurcation point and the medial pole of the condyle were 20 (5) mm and 22 (5) mm, respectively. A horizontal plane through the sigmoid notch perpendicular to the posterior border of the mandible is a good approximation of the trajectory of the MA. The branchpoint is usually within 5 mm of this line and inferior in 70% of cases. Surgeons should take note that both the branchpoint and the MA contact the surface of the mandible in a significant number of cases.


Asunto(s)
Arteria Maxilar , Cirugía Bucal , Humanos , Arteria Maxilar/diagnóstico por imagen , Radiografía , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Osteotomía Le Fort/métodos
17.
Nutrients ; 15(6)2023 Mar 09.
Artículo en Inglés | MEDLINE | ID: mdl-36986068

RESUMEN

Consumption of the total Western diet (TWD) in mice has been shown to increase gut inflammation, promote colon tumorigenesis, and alter fecal microbiome composition when compared to mice fed a healthy diet, i.e., AIN93G (AIN). However, it is unclear whether the gut microbiome contributes directly to colitis-associated CRC in this model. The objective of this study was to determine whether dynamic fecal microbiota transfer (FMT) from donor mice fed either the AIN basal diet or the TWD would alter colitis symptoms or colitis-associated CRC in recipient mice, which were fed either the AIN diet or the TWD, using a 2 × 2 factorial experiment design. Time-matched FMT from the donor mice fed the TWD did not significantly enhance symptoms of colitis, colon epithelial inflammation, mucosal injury, or colon tumor burden in the recipient mice fed the AIN diet. Conversely, FMT from the AIN-fed donors did not impart a protective effect on the recipient mice fed the TWD. Likewise, the composition of fecal microbiomes of the recipient mice was also affected to a much greater extent by the diet they consumed than by the source of FMT. In summary, FMT from the donor mice fed either basal diet with differing colitis or tumor outcomes did not shift colitis symptoms or colon tumorigenesis in the recipient mice, regardless of the basal diet they consumed. These observations suggest that the gut microbiome may not contribute directly to the development of disease in this animal model.


Asunto(s)
Colitis , Trasplante de Microbiota Fecal , Ratones , Animales , Carcinogénesis , Transformación Celular Neoplásica , Inflamación , Dieta Occidental , Ratones Endogámicos C57BL
18.
Entropy (Basel) ; 25(1)2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36673263

RESUMEN

In this paper, the security of two-way relay communications in the presence of a passive eavesdropper is investigated. Two users communicate via a relay that depends solely on energy harvesting to amplify and forward the received signals. Time switching is employed at the relay to harvest energy and obtain user information. A friendly jammer is utilized to hinder the eavesdropping from wiretapping the information signal. The eavesdropper employs maximal ratio combining and selection combining to improve the signal-to-noise ratio of the wiretapped signals. Geometric programming (GP) is used to maximize the secrecy capacity of the system by jointly optimizing the time switching ratio of the relay and transmit power of the two users and jammer. The impact of imperfect channel state information at the eavesdropper for the links between the eavesdropper and the other nodes is determined. Further, the secrecy capacity when the jamming signal is not perfectly cancelled at the relay is examined. The secrecy capacity is shown to be greater with a jammer compared to the case without a jammer. The effect of the relay, jammer, and eavesdropper locations on the secrecy capacity is also studied. It is shown that the secrecy capacity is greatest when the relay is at the midpoint between the users. The closer the jammer is to the eavesdropper, the higher the secrecy capacity as the shorter distance decreases the signal-to-noise ratio of the jammer.

19.
Oral Maxillofac Surg ; 27(1): 131-139, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35066650

RESUMEN

PURPOSE: The aim of this study was to undertake a 5-year review of the OMX temporomandibular prosthetic total joint replacement system (OMX-TMJ). METHODS: Data was collected from patients who had an OMX-TMJ implanted between May 2015 and November 2020 at Epworth-Freemasons and St. Vincent's hospitals in Melbourne, Australia. The data points included patient demographics, primary diagnosis, and clinical outcomes in terms of visual analogue scale (VAS) for pain, maximum inter-incisal mouth opening, and complication events. RESULTS: There were 206 OMX-TMJ devices implanted in 151 patients over the 5-year study period. The vast majority were female patients (n = 137, 90.7%) with a mean age of 44.8 years (range 20-76 years) at the time of surgery. Most patients presented with primary (idiopathic) osteoarthritis (119 joints-57.8%) that failed to respond to conservative measures. Based on a mean follow-up period of 36 months (range 12 months to 73 months), the average mouth opening improved from 30.8 mm pre-surgery to an average of 39.1 mm following OMX-TMJ surgery (p < 0.05). Joint pain (VAS: 0-10) significantly improved from 6.14 pre-surgery to 0.87 following OMX-TMJ surgery (p < 0.001). Twenty-one patients (13.9%) experienced device-related complications which resulted in explantation of 7 (3.4%) OMX-TMJ devices over the 5-year period. CONCLUSION: This study shows that the OMX-TMJ prosthetic total joint replacement system is a reasonably safe, versatile, and reliable implant that effectively improves mandibular opening and reduces joint pain across a broad range of end-stage TMJ disorders.


Asunto(s)
Artroplastia de Reemplazo , Prótesis Articulares , Trastornos de la Articulación Temporomandibular , Humanos , Masculino , Femenino , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Articulación Temporomandibular/cirugía , Trastornos de la Articulación Temporomandibular/cirugía , Artroplastia de Reemplazo/métodos , Mandíbula/cirugía , Resultado del Tratamiento , Rango del Movimiento Articular
20.
Health Aff Sch ; 1(4): qxad047, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38756741

RESUMEN

Variation in availability, format, and standardization of patient attributes across health care organizations impacts patient-matching performance. We report on the changing nature of patient-matching features available from 2010-2020 across diverse care settings. We asked 38 health care provider organizations about their current patient attribute data-collection practices. All sites collected name, date of birth (DOB), address, and phone number. Name, DOB, current address, social security number (SSN), sex, and phone number were most commonly used for cross-provider patient matching. Electronic health record queries for a subset of 20 participating sites revealed that DOB, first name, last name, city, and postal codes were highly available (>90%) across health care organizations and time. SSN declined slightly in the last years of the study period. Birth sex, gender identity, language, country full name, country abbreviation, health insurance number, ethnicity, cell phone number, email address, and weight increased over 50% from 2010 to 2020. Understanding the wide variation in available patient attributes across care settings in the United States can guide selection and standardization efforts for improved patient matching in the United States.

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