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1.
Appetite ; : 107603, 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-39002565

RESUMEN

Intuitive eating is an adaptive eating approach shown to have positive psychological and physical health outcomes. Understanding the motivation behind eating behavior can provide valuable information for why some women eat intuitively and others do not. Using self-determination theory (SDT), this study aimed to identify motivational profiles for eating behavior and examine differences in intuitive eating across these motivational profiles. A nationally representative sample of New Zealand women (n = 1,447) aged 40 to 50 years (M = 45.4; SD = 3.2) completed questionnaires assessing motivation and intuitive eating. Latent profile analysis identified five profiles characterized by varying levels of the global and specific forms of behavioral regulation described by SDT. The self-determined profile, characterized by high levels of global self-determination, had higher intuitive eating scores. The internalized profile, characterized by high levels of identified and integrated regulation, had average intuitive eating scores. The conflicted profile, characterized by high levels on most forms of behavioral regulation, and the unmotivated profile, characterized low levels on all forms of behavioral regulation, had a mix of high and low intuitive eating subscale scores. The amotivated profile, characterized by very high levels of amotivation, had lower intuitive eating scores. A motivational profile characterized by higher levels of self-determination and lower levels of the extrinsic forms of behavioral regulation appears to be beneficial for intuitive eating. Therefore, SDT-informed eating behavior interventions that enhance women's self-determined motivation should be created to facilitate intuitive eating in midlife women.

2.
J Dairy Sci ; 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39004130

RESUMEN

Antimicrobial use (AMU) data are essential for monitoring usage over time, facilitating reduction strategies to combat the threat of antimicrobial resistance (AMR) to both human and animal health. The objective of this study was to measure and describe AMU over a 12-mo period in Irish dairy herds and compare 3 different recording methods to a reference method. A sample of 33 Irish dairy herds were randomly selected from 6 private veterinary practices across Ireland. The herds were followed for a 12-mo period and their AMU was monitored using 3 recording methods: 1. Veterinary prescription data (VET), 2. The inventory of medicine bins on the farms (BIN), and 3. Farmer treatment records from herd recording software (APP). Each recording method was compared with a previously developed reference method for AMU. The reference method used was based on pre- and poststudy medicine stock on the farms combined with veterinary prescription data. Antimicrobial use was analyzed using both mass- and dosed-based metrics, including mass (mg) of antimicrobial active ingredient per population correction unit (mg/PCU), defined daily doses for animals (DDDVET) and defined course doses for animals (DCDVET). Median AMU was 16.24, 10.47, 8.87 and 15.55 mg/PCU by mass, and 2.43, 1.55, 1.19 and 2.26 DDDVET by dose for VET, BIN, APP, and reference method data, respectively. Reliability of the agreement between each pair of methods was quantified using the concordance correlation coefficient (CCC). When compared with the reference method, VET data had excellent reliability [95% confidence interval (CI) of CCC: 0.992-0.998]. The BIN data had good to excellent reliability [95% CI of CCC: 0.776-0.936]. The APP data had poor reliability when compared with the reference method [95% CI of CCC: -0.167-0.156]. Our results highlight that a small number of herds were contributing most to overall use and farmers showed varying levels of consistency in recording AMU. Veterinary data were the most reliable approach for assessing AMU when compared with a reference method of AMU. This is an important finding for the future monitoring of AMU at a national level.

3.
PM R ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38695509

RESUMEN

BACKGROUND: Survivors of hospitalization for severe acute COVID-19 infection faced significant functional impairments necessitating discharge to inpatient rehabilitation facilities (IRFs) for intensive rehabilitation prior to discharge home. There remains a lack of large cohort studies of the functional outcomes of patients admitted to IRFs with COVID-19-related impairments and the relationship to patient-specific factors. OBJECTIVE: To characterize functional outcomes of patients admitted to IRFs for COVID-19-related debility and to investigate associations between functional outcomes and patient-specific factors. DESIGN: Multisite retrospective cohort study. SETTING: Multiple IRFs in a large urban city. PARTICIPANTS: Adult patients admitted to IRFs for rehabilitation after hospitalization for acute COVID-19 infection. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary outcomes included change in GG Self-Care and Mobility Activities subscales and Functional Independence Measure scores from admission to discharge from inpatient rehabilitation. Linear regression analysis was used to relate functional changes to demographic, medical, and hospitalization-specific factors. Secondary outcomes included discharge destination from the IRF. RESULTS: The analysis included n = 362 patients admitted to IRFs for COVID-19-related rehabilitation needs. This cohort showed significant improvements in mobility, self-care, and cognition congregate scores (216.0%, 174.3%, 117.6% respectively). Patient-specific factors associated with functional improvement, included age, body mass index, premorbid employment status, history of diabetes and cardiac disease and medications received in acute care, and muscle strength upon admission to IRF. CONCLUSIONS: Patients admitted to inpatient rehabilitation for COVID-19-related functional deficits made significant functional improvements in mobility, self-care, and cognition. Many significant associations were found between patient-specific factors and functional improvement, which support further investigation of these factors as possible predictors of functional improvement in an IRF for COVID-19-related deficits.

4.
PM R ; 2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38520158

RESUMEN

BACKGROUND: Neighborhoods with more social determinants of health (SDOH) risk factors have higher rates of infectivity, morbidity, and mortality from COVID-19. Patients with severe COVID-19 infection can have long-term functional deficits leading to lower quality of life (QoL) and independence measures. Research shows that these patients benefit greatly from inpatient rehabilitation facilities (IRF) admission, but there remains a lack of studies investigating long-term benefits of rehabilitation once patients are returned to their home environment. OBJECTIVE: To determine SDOH factors related to long-term independence and QoL of COVID-19 patients after IRF stay. DESIGN: Multisite cross-sectional survey. SETTING: Two urban IRFs. MAIN OUTCOME MEASURES: Primary outcome measures were Post-COVID Functional Status Scale (PCFS) and Short Form-36 (SF-36) scores. Secondary outcomes were quality indicator (QI) scores while at IRF and a health care access questionnaire. Results were analyzed using analysis of variance and multivariate logistic regression analyses. RESULTS: Participants (n = 48) who were greater than 1 year post-IRF stay for severe COVID-19 were enrolled in the study. Higher SF-36 scores were associated with male gender (p = .002), higher income (≥$70,000, p = .004), and living in the city (p = .046). Similarly, patients who were of the male gender (p = .004) and had higher income (≥$70,000, p = .04) had a greater odds of a 0 or 1 on the PCFS. Age was not associated with differences. Women were more likely to seek follow-up care (p = .014). Those who sought follow-up care reported lower SF-36 overall and emotional wellness scores, p = .041 and p = .007, respectively. Commonly reported barriers to health care access were financial and time constraints. CONCLUSIONS: Patients with SDOH risk factors need to be supported in the outpatient setting to maintain functional gains made during IRF stays. Female gender, income, and urban setting are potential predictors for long-term QoL and independence deficits after rehabilitation for COVID-19 infection. Low emotional wellness is an indicator for patients to seek out care as far out as 1 year from their rehabilitation stay.

5.
Clin Pediatr (Phila) ; : 99228241227756, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38334063

RESUMEN

Parents (N = 599) of 6-month-old to 10-year-old children were given a handbook intervention that educates about healthy discipline in a pediatric clinic serving low-income families in Nashville, Tennessee. A research assistant spent approximately 1 minute introducing the intervention. A total of 440 parents (73.4%) responded to a follow-up survey 2 to 4 months later. Most parents (88%) who completed the follow-up survey had read at least part of the handbook. Of parents who received the handbook, 63% reported that the handbook helped them discipline their children. Half of parents reported specific changes they made because of the handbook. The most frequently reported changes were more talking/explaining/communicating (25%), more redirecting (7.8%), more patience/listening (6.0%), less anger/yelling (10.8%), and less spanking (7.5%). 42% of parents reported that they shared the handbook with other caregivers, friends, relatives, and children. A brief clinic intervention improves parents' discipline practices and reaches other caregivers.

6.
J Dairy Sci ; 107(7): 5001-5015, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38395392

RESUMEN

Antimicrobial use (AMU) data are essential to monitor the effect of AMU reduction strategies in animal health. The use of technology and herd recording software to record AMU will be vital to scale the collation of these data in the future. The aim of this study was to determine the barriers and facilitators to Irish dairy farmers recording their AMU using a herd recording software and sharing AMU data. Thirty-three Irish dairy farmers involved in a study on AMU monitoring were asked to record their AMU using a herd recording software over a 12-mo period. At the end of the 12-mo period, 10 of these farmers were selected to take part in semi-structured interviews exploring their opinions on recording AMU, the use of herd recording software, and sharing AMU data. Interviews were transcribed and qualitatively analyzed using inductive thematic analysis. Several barriers and facilitators to farmers recording their AMU using a herd recording software and sharing AMU data were identified. Barriers included the age and generation of the farmer, farm infrastructure, a lack of training and education, a lack of knowledge around the benefits of digital data, a lack of incentive to digitize records, and a fear of repercussions. Facilitators identified by the farmers included the benefits of having instantly available data for making herd management decisions, reduced paperwork, increased organization for inspections, and a potential positive effect on the image of the dairy industry. To increase the uptake of new technology to record AMU at farm-level, farmers will need support in terms of education and training around the software available to them and reassurance around the perceived risks of repercussions with sharing data in a digital format.


Asunto(s)
Antiinfecciosos , Industria Lechera , Granjas , Animales , Bovinos , Agricultores , Irlanda
7.
Nat Cancer ; 5(3): 420-432, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38172341

RESUMEN

Checkpoint inhibition (CPI), particularly that targeting the inhibitory coreceptor programmed cell death protein 1 (PD-1), has transformed oncology. Although CPI can derepress cancer (neo)antigen-specific αß T cells that ordinarily show PD-1-dependent exhaustion, it can also be efficacious against cancers evading αß T cell recognition. In such settings, γδ T cells have been implicated, but the functional relevance of PD-1 expression by these cells is unclear. Here we demonstrate that intratumoral TRDV1 transcripts (encoding the TCRδ chain of Vδ1+ γδ T cells) predict anti-PD-1 CPI response in patients with melanoma, particularly those harboring below average neoantigens. Moreover, using a protocol yielding substantial numbers of tissue-derived Vδ1+ cells, we show that PD-1+Vδ1+ cells display a transcriptomic program similar to, but distinct from, the canonical exhaustion program of colocated PD-1+CD8+ αß T cells. In particular, PD-1+Vδ1+ cells retained effector responses to TCR signaling that were inhibitable by PD-1 engagement and derepressed by CPI.


Asunto(s)
Neoplasias , Subgrupos de Linfocitos T , Humanos , Subgrupos de Linfocitos T/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Perfilación de la Expresión Génica , Inmunoterapia
8.
Chem Commun (Camb) ; 60(6): 758-761, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38126447

RESUMEN

Incremental, single-atom substitutions of Se-based chalcogen bond (Ch-bond) donors with stronger donating Te centers were implemented in two new triptycene tris(1,2,5-chalcogenadiazole) tectons. The appreciably more favorable Ch-bonding ability of the Te-based donors promotes assembly of low-density networks and more stable Ch-bonded organic frameworks (ChOFs).

9.
bioRxiv ; 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-38045305

RESUMEN

In amniotes, head motions and tilt are detected by two types of vestibular hair cells (HCs) with strikingly different morphology and physiology. Mature type I HCs express a large and very unusual potassium conductance, gK,L, which activates negative to resting potential, confers very negative resting potentials and low input resistances, and enhances an unusual non-quantal transmission from type I cells onto their calyceal afferent terminals. Following clues pointing to KV1.8 (KCNA10) in the Shaker K channel family as a candidate gK,L subunit, we compared whole-cell voltage-dependent currents from utricular hair cells of KV1.8-null mice and littermate controls. We found that KV1.8 is necessary not just for gK,L but also for fast-inactivating and delayed rectifier currents in type II HCs, which activate positive to resting potential. The distinct properties of the three KV1.8-dependent conductances may reflect different mixing with other KV1 subunits, such as KV1.4 (KCNA4). In KV1.8-null HCs of both types, residual outwardly rectifying conductances include KV7 (KCNQ) channels. Current clamp records show that in both HC types, KV1.8-dependent conductances increase the speed and damping of voltage responses. Features that speed up vestibular receptor potentials and non-quantal afferent transmission may have helped stabilize locomotion as tetrapods moved from water to land.

10.
Disabil Rehabil ; : 1-11, 2023 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-37970845

RESUMEN

PURPOSE: The ways in which words are used to describe and discuss people with disabilities has long been an area of social concern. Previous research has demonstrated that language can overtly and subtly influence cognitions and perceptions of individuals, but there is less research on how language relates to perceptions of individuals with disabilities. MATERIALS AND METHODS: A content analysis of 236 peer-reviewed articles was performed to explore differences in the frequency of the use of "disability," "disorder," and "illness" in academic articles related to eight common conditions: deafness, blindness, multiple sclerosis, quadriplegia, anxiety, depression, schizophrenia, and addiction. RESULTS: Results indicated that there were differences in how disability language was used by academic writers. Specifically, "disability" appeared in the writing more frequently in articles related to physical disabilities, "disorder" appeared most frequently in articles related to anxiety and depression, and "illness" appeared most frequently in articles related to schizophrenia. CONCLUSIONS: This observed difference in frequency use could reflect differences in the context and meaning of the use of these conditions. Suggestions for future research are discussed.


The way individuals write and talk about conditions may indicate the way they think about the conditions.When compared to articles written about physical conditions, the term "disability" is used less by academic writers than when discussing mental conditions.This suggests that academic writers may view mental conditions as less "prototypical" disabilities (compared to physical conditions).Careful consideration should be given to the language used when discussing all types of disabilities.When writers, media professionals, policymakers, and the public are educated on the diverse range of conditions and the unique challenges they present to individuals, only then can rehabilitation be truly comprehensive and effective.

11.
Foot Ankle Spec ; : 19386400231208518, 2023 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-37942785

RESUMEN

Although hammertoe (HT) is a common complaint among foot patients, there is little consensus on the best surgical approach for correction. These authors hypothesized that the use of a headless intramedullary screw across both the proximal interphalangeal joint (PIPJ) and distal interphalangeal joint (DIPJ) would decrease many post-surgical complications, such as infection, pain, and mallet toe deformity, found in traditional HT corrective surgical techniques. In this retrospective cohort study, N = 163 adult patients who had undergone DIPJ/PIPJ arthrodesis for HT correction at least 1 year prior to the study were identified. One hundred fifty-nine patients were contacted through REDCap to complete Patient-Reported Outcome Measurement Information System (PROMIS) physical function (PF) and pain interference (PI). Demographic, radiographic, and follow-up data were taken from the electronic medical record (EMR). Analysis was completed with Microsoft Excel; PROMIS PF and PI measures for the 32-person cohort were 45.65 ± 8.26 and 51.65 ± 9.01, respectively. The PF and PI measures had a statistically significant correlation (R2 = 0.71). The 163-person cohort had an overall revision rate of 6.75%, or 11 patients, and an infection rate of 1.23%. This procedure had lower rates of residual pain, infection, mallet toe deformity, and reoperation when compared with current techniques. This study supports the safety and viability of PIPJ/DIPJ arthrodesis using a headless screw for HT correction.Levels of Evidence: Level III Retrospective Cohort Study.

12.
Int J Pharm ; 644: 123341, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37611854

RESUMEN

Conductive olfaction and nose to brain drug delivery are important processes that remain limited by inadequate odorant or drug delivery to the olfactory airspace. Primary challenges include anatomic barriers and poor targeting to the olfactory region. This study uses computational fluid dynamics to investigate the effects of nasal midvault surgery on olfactory drug delivery with intranasal sprays. Soft tissue elevation, spreader flaps, and spreader grafts were performed on two fresh cadaveric specimens, using computed tomography for airway reconstruction. Nasal airflow and drug particle transport simulations were performed under these conditions: inhalation rate (15, 30 L/min), spray velocity (1, 5, 10 m/s), spray location (top, bottom, center, medial, lateral), head position (upright, supine, forward, backward), and particle size (1-100 µm). Simulation results were used to calculate drug particle deposition to the olfactory airspaces and bulbs. Total olfactory deposition was < 5% but attained a maximum of 36.33% when sorted by particle size. There was no association between nasal midvault surgery and olfactory deposition. No single parameter or technique demonstrated superior olfactory deposition, but smaller particle size, slower spray velocity, and higher inhalation rate tended to optimize olfactory deposition, providing important implications for future intranasal spray and drug design to target the olfactory airspace.


Asunto(s)
Sistemas de Liberación de Medicamentos , Olfato , Humanos , Nariz , Transporte Biológico , Encéfalo
13.
PLoS One ; 18(7): e0285349, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37523365

RESUMEN

BACKGROUND: Parkinson's disease has been identified as a risk factor for severe Coronavirus disease 2019 (COVID-19) outcomes. However, whether the significant high risk of death from COVID-19 in people with Parkinson's disease is specific to the disease itself or driven by other concomitant and known risk factors such as comorbidities, age, and frailty remains unclear. OBJECTIVE: To investigate clinical profiles and outcomes of people with Parkinson's disease and atypical parkinsonian syndromes who tested positive for COVID-19 in the hospital setting in a multicentre UK-based study. METHODS: A retrospective cohort study of Parkinson's disease patients with a positive SARS-CoV-2 test admitted to hospital between February 2020 and July 2021. An online survey was used to collect data from clinical care records, recording patient, Parkinson's disease and COVID-19 characteristics. Associations with time-to-mortality and severe outcomes were analysed using either the Cox proportional hazards model or logistic regression models, as appropriate. RESULTS: Data from 552 admissions were collected: 365 (66%) male; median (inter-quartile range) age 80 (74-85) years. The 34-day all-cause mortality rate was 38.4%; male sex, increased age and frailty, Parkinson's dementia syndrome, requirement for respiratory support and no vaccination were associated with increased mortality risk. Community-acquired COVID-19 and co-morbid chronic neurological disorder were associated with increased odds of requiring respiratory support. Hospital-acquired COVID-19 and delirium were associated with requiring an increase in care level post-discharge. CONCLUSIONS: This first, multicentre, UK-based study on people with Parkinson's disease or atypical parkinsonian syndromes, hospitalised with COVID-19, adds and expands previous findings on clinical profiles and outcomes in this population.


Asunto(s)
COVID-19 , Fragilidad , Enfermedad de Parkinson , Trastornos Parkinsonianos , Humanos , Masculino , Anciano de 80 o más Años , Femenino , COVID-19/epidemiología , SARS-CoV-2 , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Estudios Retrospectivos , Cuidados Posteriores , Alta del Paciente , Trastornos Parkinsonianos/complicaciones , Trastornos Parkinsonianos/epidemiología , Reino Unido/epidemiología
15.
Ir Vet J ; 76(1): 8, 2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-37009876

RESUMEN

BACKGROUND: In the coming years, major governance changes in the form of policy directives and regulations will catalyse major top-down change with respect to animal health on European farms in an effort to combat the OneHealth threat of antimicrobial resistance. This top-down approach must be met with bottom-up strategies to ensure target actors (namely, farmers and vets) are supported and motivated to change their practices, thus, avoiding unintended consequences of forced change. Although much behavioural research has explored the factors influencing antimicrobial practices on farms, a gap exists translating these findings into evidence-based behaviour change interventions that can be put into practice. The current study aims to fill this gap. It provides insights into identifying, understanding, and changing the behaviours of farmers and veterinarians with respect to the responsible use of antimicrobials in farming. RESULTS: Through an inter-disciplinary and multi-actor approach, the study combines scientific knowledge from the behavioural sciences and animal health sciences, coupled with tacit knowledge from a co-design, participatory approach to recommend seven behaviour change interventions that can help to support good practices amongst farmers and vets, with respect to animal health, and reduce the use of antimicrobials on farms. The behaviour change interventions include message framing; OneHealth awareness campaign; specialised communications training; on-farm visual prompts and tools; social support strategies (for both farmers and vets); and antimicrobial use monitoring. The study details each intervention with respect to their evidence base and scientific concept, grounded in behavioural science, along with stakeholder feedback on design and delivery of the interventions. CONCLUSIONS: These behaviour change interventions can be taken, adapted, and put into practice by the agri-food community to support good animal health practices and responsible antimicrobial use on farms.

16.
Nat Commun ; 14(1): 2308, 2023 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-37085489

RESUMEN

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (~30 kb). Here, we present a plasmid-based viral genome assembly and rescue strategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.


Asunto(s)
COVID-19 , Proteínas de la Nucleocápside de Coronavirus , SARS-CoV-2 , Animales , Proteínas de la Nucleocápside de Coronavirus/genética , Genoma Viral/genética , ARN Viral/genética , SARS-CoV-2/genética , ARN Subgenómico/genética
17.
Nat Commun ; 14(1): 1613, 2023 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-36959176

RESUMEN

Dopamine has a significant role in motor and cognitive function. The dopaminergic pathways originating from the midbrain have received the most attention; however, the relevance of the cerebellar dopaminergic system is largely undiscovered. Here, we show that the major cerebellar astrocyte type Bergmann glial cells express D1 receptors. Dopamine can be synthesized in Purkinje cells by cytochrome P450 and released in an activity-dependent fashion. We demonstrate that activation of D1 receptors induces membrane depolarization and Ca2+ release from the internal store. These astrocytic activities in turn modify Purkinje cell output by altering its excitatory and inhibitory synaptic input. Lastly, we show that conditional knockout of D1 receptors in Bergmann glial cells results in decreased locomotor activity and impaired social activity. These results contribute to the understanding of the molecular, cellular, and circuit mechanisms underlying dopamine function in the cerebellum, revealing a critical role for the cerebellar dopaminergic system in motor and social behavior.


Asunto(s)
Astrocitos , Células de Purkinje , Células de Purkinje/fisiología , Astrocitos/metabolismo , Dopamina/metabolismo , Cerebelo , Neuroglía/fisiología
18.
bioRxiv ; 2023 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-36798416

RESUMEN

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (30kb). Here, we designed a plasmid-based viral genome assembly and resc ue strategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.

19.
Laryngoscope ; 133(5): 1036-1043, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-35560998

RESUMEN

OBJECTIVES: To determine parameter combinations for effective drug delivery of intranasal spray steroids to the ostiomeatal complex (OMC) and maxillary sinus (MS) in patients with chronic rhinosinusitis (CRS). METHODS: Each patient's sinonasal cavity was reconstructed from computed tomography scans. Intranasal airflow and drug particle transport were simulated using computational fluid dynamic modeling. Airflow simulations were performed at 15 Pascal inhalation pressure. Intranasal spray particles of 1-100 µm were simulated at release speeds of 1, 5, and 10 m/s from 6 release locations (Bottom, Center, Top, Lateral, Lateral-Bottom, and Lateral-Top) at a nozzle insertion depth of 15 mm. Drug delivery simulations were performed in the head tilted forward position. RESULTS: Maximal OMC deposition was 0.78%-12.44%, while maximal MS deposition was 0.02%-1.03% across all simulations. In general, particles between 6 and 10 µm had the best OMC (at 1 m/s particle velocity) and MS (at 10 m/s particle velocity) deposition. Particles ranging from 21 to 30 µm also had superior OMC deposition. The lateral and lateral-top spray release locations produced maximum OMC deposition, but no one release location demonstrated an increase in MS deposition. CONCLUSION: This preliminary study suggests that it is challenging to determine a common set of intranasal spray parameter combinations for effective drug delivery to the OMC and MSs. Although drug particle size and spray particle velocity seem to impact particle deposition patterns, spray release location appears to vary with anatomical differences between subjects, particularly when the MS is the target location for particle deposition. Laryngoscope, 133:1036-1043, 2023.


Asunto(s)
Sinusitis , Humanos , Sinusitis/tratamiento farmacológico , Administración Intranasal , Preparaciones Farmacéuticas , Seno Maxilar , Simulación por Computador , Enfermedad Crónica , Tamaño de la Partícula , Aerosoles y Gotitas Respiratorias
20.
Laryngoscope Investig Otolaryngol ; 7(5): 1626-1633, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36258861

RESUMEN

Objectives/hypothesis: The objective of this study is to describe long-term hearing outcomes in infants born to mothers with a known cytomegalovirus (CMV) positivity who were not tested for congenital CMV. Study type: Clinical research study. Design: Retrospective cohort study. Methods: Retrospective chart review was performed for mothers seropositive to CMV. Mother-infant dyads (130) were identified between January 1, 2013 and January 1, 2017. Outcomes data was collected through June 1, 2020. Demographics, risk factors for hearing loss, evidence of CMV infection, other causes of hearing loss, need for speech therapy services, and results of all hearing tests were collected. Results: All 130 infants were asymptomatic and 5 were tested for congenital CMV. Five were negative for CMV and excluded from analyses. Of the remaining 125, only 1 had low-viral avidity IgG antibodies. None had IgM antibodies. Four children (3.2%) had hearing loss at last audiogram and one child had delayed onset SNHL due to an enlarged vestibular aqueduct. Speech therapy for communication was required for 33 children (26.4%). Conclusions: Knowledge of maternal perinatal CMV status can allow for education about possible sequelae of cCMV, as well as trigger an alert for testing babies born to mothers with low-viral avidity IgG during the first trimester, when the risk of vertical transmission is highest. Also, babies born to CMV positive mothers may be more at risk for communication delays necessitating intervention. Studies focusing on the impact of maternal CMV related to childhood communication deficits could elucidate any direct relationships.

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