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1.
J Prev Alzheimers Dis ; 11(2): 320-328, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374738

RESUMO

BACKGROUND: There is limited literature regarding the impact of differential rates of disease progression on longitudinal outcomes in individuals with early Alzheimer's disease (AD) and confirmed brain amyloid pathology. OBJECTIVES: To describe the underlying characteristics and long-term outcomes associated with different rates of disease progression among amyloid-positive individuals with early symptomatic AD. DESIGN: Retrospective observational study. SETTING: Data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) in the United States (06/2005-11/2021). PARTICIPANTS: Individuals with a clinical assessment of mild cognitive impairment or dementia and Clinical Dementia Rating® Dementia Staging Instrument Sum of Boxes (CDR-SB) score 0.5-9.0 (inclusive; first visit defined as the index date) and confirmed amyloid positivity. Participants were stratified into No Progression (change ≤0), Slower Progression (0< change <2.0 points), Median Progression (2.0-point change), and Faster Progression (change >2.0 points) cohorts based on the observed distribution of changes in CDR-SB score between the index and first subsequent visit. MEASUREMENTS: For each cohort, the functional and neuropsychiatric outcomes were described at index and each subsequent visit for up to five years, and least-square (LS) mean changes from baseline were estimated using linear mixed-effects models adjusting for baseline demographic and clinical characteristics. RESULTS: Among 1,263 participants included in the analysis, the mean±standard deviation (SD) age at index was 72.7±9.7 years and 55.3% were males. Demographic characteristics and comorbidity profiles at index were similar across cohorts. However, at index, the Faster Progression (N=279) cohort had higher CDR-SB and Functional Assessment Questionnaire (FAQ) scores compared with the No Progression (N=474), Slower Progression (N=297), and Median Progression (N=213) cohorts. Adjusting for baseline characteristics, at year 5 after index the FAQ score increased by 23.6 points for Faster Progression cohort and 10.4, 15.8, and 19.2 points for the No, Slower, and Median Progression cohorts, respectively. The corresponding increases in Neuropsychiatric Inventory Questionnaire (NPI-Q) scores were 6.7 points for the Faster Progression cohort, and by 1.3, 3.1, and 8.3 points, for the No, Slower, and Median Progression cohorts, respectively. CONCLUSIONS: Despite similar demographic and clinical profiles at baseline, amyloid-positive individuals with greater deterioration based on CDR-SB early in the AD trajectory continue to experience worse functional and behavioral outcomes over time than those with more gradual deterioration in this metric.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Feminino , Humanos , Masculino , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/patologia , Estudos de Coortes , Progressão da Doença , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos
2.
J Prev Alzheimers Dis ; 11(2): 310-319, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374737

RESUMO

BACKGROUND: Emerging therapies have shown promising results for slowing the progression of Alzheimer's disease (AD). However, the potential impact of these therapies on real-world outcomes remains to be explored. OBJECTIVE: To examine the impact of slowing AD progression on functional abilities and behavioral symptoms. DESIGN: Retrospective observational study. SETTING: Data from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) in the United States (06/2005-11/2021, primary analysis) and the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (09/2005-03/2022, sensitivity analysis) were used. PARTICIPANTS: Individuals with mild cognitive impairment (MCI) or mild dementia, Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score 0.5-9.0 (inclusive; first visit defined as the index date), and confirmed amyloid positivity were identified in NACC. In ADNI, individuals with at least one clinical center visit with a clinical assessment of MCI or mild dementia and confirmed amyloid positivity were identified. MEASUREMENTS: Hypothetical effects of slowing disease progression as assessed by CDR-SB on functional and behavioral outcomes including the Functional Activities Questionnaire (FAQ) score, Neuropsychiatric Inventory Questionnaire (NPI-Q) score, and the probability of complete dependence over five years were evaluated using multivariable regression among NACC participants, separately for the subgroups with MCI and mild dementia at baseline, respectively. For the ADNI sensitivity analysis, the hypothetical effects of slowing disease progression were evaluated for FAQ score using multivariable regression among the MCI participants only. RESULTS: Compared with natural disease progression, slowing progression by 20% over five years for NACC participants with MCI and mild dementia, respectively, would result in 1.7-point (10.8%) and 1.6-point (12.9%) less deterioration based on FAQ; 0.5-point (20.3%) and 0.5-point (19.3%) less deterioration based on NPI-Q; 4.7 percentage-point (22.2%) and 10.1 percentage-point (21.6%) lower probability of complete dependence. Among ADNI participants, delaying disease progression by 20% or 30% over 4 years would avert deterioration based on FAQ of 1.1 points (20.4%) and 1.6 points (29.6%), respectively, compared to natural disease progression. CONCLUSIONS: Slowing early AD progression could result in preservation of functional and behavioral attributes and functional autonomy for longer.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Demência , Humanos , Doença de Alzheimer/diagnóstico , Demência/diagnóstico , Disfunção Cognitiva/diagnóstico , Amiloide , Progressão da Doença
3.
Front Pharmacol ; 14: 1244580, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074149

RESUMO

Postpartum depression affects many individuals after parturition, and selective serotonin reuptake inhibitors (SSRIs) are often used as the first-line treatment; however, both SSRIs and lactation are independently associated with bone loss due to the role of serotonin in bone remodeling. Previously, we have established that administration of the SSRI fluoxetine during the peripartal period results in alterations in long-term skeletal characteristics. In the present study, we treated mice with either a low or high dose of fluoxetine during lactation to determine the consequences of the perturbation of serotonin signaling during this time period on the dam skeleton. We found that lactational fluoxetine exposure affected both cortical and trabecular parameters, altered gene expression and circulating markers of bone turnover, and affected mammary gland characteristics, and that these effects were more pronounced in the dams that were exposed to the low dose of fluoxetine in comparison to the high dose. Fluoxetine treatment during the postpartum period in rodents had short term effects on bone that were largely resolved 3 months post-weaning. Despite the overall lack of long-term insult to bone, the alterations in serotonin-driven lactational bone remodeling raises the question of whether fluoxetine is a safe option for the treatment of postpartum depression.

4.
J Biol Chem ; 299(12): 105474, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37981209

RESUMO

G protein-coupled receptor (GPCR) signaling and trafficking are regulated by multiple mechanisms, including posttranslational modifications such as ubiquitination by E3 ubiquitin ligases. E3 ligases have been linked to agonist-stimulated ubiquitination of GPCRs via simultaneous binding to ßarrestins. In addition, ßarrestins have been suggested to assist E3 ligases for ubiquitination of key effector molecules, yet mechanistic insight is lacking. Here, we developed an in vitro reconstituted system and show that ßarrestin1 (ßarr1) serves as an adaptor between the effector protein signal-transducing adaptor molecule 1 (STAM1) and the E3 ligase atrophin-interacting protein 4. Via mass spectrometry, we identified seven lysine residues within STAM1 that are ubiquitinated and several types of ubiquitin linkages. We provide evidence that ßarr1 facilitates the formation of linear polyubiquitin chains at lysine residue 136 on STAM1. This lysine residue is important for stabilizing the ßarr1:STAM1 interaction in cells following GPCR activation. Our study identifies atrophin-interacting protein 4 as only the second E3 ligase known to conjugate linear polyubiquitin chains and a possible role for linear ubiquitin chains in GPCR signaling and trafficking.


Assuntos
Poliubiquitina , Ubiquitina-Proteína Ligases , beta-Arrestina 1 , Lisina/metabolismo , Poliubiquitina/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , beta-Arrestina 1/metabolismo
5.
Physiol Rep ; 11(23): e15881, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38031314

RESUMO

At the end of gestation, fetal skeleton rapidly accumulates calcium, and bone development continues in offspring postnatally. To accommodate, maternal skeletal physiology is modulated in a serotonin-dependent manner. Selective serotonin reuptake inhibitors (SSRIs) are generally considered safe for treatment of major depressive disorder, postpartum depression, and other psychiatric illnesses during the peripartum period, but because serotonin affects bone remodeling, SSRIs are associated with decreased bone mass across all ages and sexes, and the impact of SSRIs during fetal and postnatal development has not been fully investigated. In the present study, our aim was to examine developmental fluoxetine exposure on offspring skeleton and to assess varying degrees of impact depending on dose and window of exposure in short-term and long-term contexts. We established that a low dose of lactational fluoxetine exposure caused a greater degree of insult to offspring bone than either a low dose during fetal and postpartum development or a high dose during lactation only in mice. We further discovered lasting impacts of developmental fluoxetine exposure, especially during lactation only, on adult bone and body composition. Herein, we provide evidence fluoxetine exposure during early development may have detrimental effects on the skeleton of offspring at weaning and into adulthood.


Assuntos
Transtorno Depressivo Maior , Efeitos Tardios da Exposição Pré-Natal , Feminino , Camundongos , Animais , Humanos , Fluoxetina/toxicidade , Inibidores Seletivos de Recaptação de Serotonina/toxicidade , Transtorno Depressivo Maior/tratamento farmacológico , Serotonina , Osso e Ossos , Efeitos Tardios da Exposição Pré-Natal/tratamento farmacológico
6.
Phys Chem Chem Phys ; 25(47): 32613-32621, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38009218

RESUMO

A relativistic coupled-cluster study of the low-lying electronic states in the radium monohydroxide molecule (RaOH), a radioactive polyatomic molecule of interest to laser cooling and to the search of new physics beyond the Standard Model, is reported. The level positions of the A2Π1/2 and C2Σ states have been computed with an accuracy of around 200 cm-1 to facilitate spectroscopic observation of RaOH using laser induced fluorescence spectroscopy, thereby exploiting the systematic convergence of electron-correlation and basis-set effects in relativistic coupled-cluster calculations. The energy level for the B2Δ3/2 state has also been calculated accurately to conclude that the B2Δ3/2 state lies above the A2Π1/2 state. This confirms X2Σ â†” A2Π1/2 as a promising optical cycling transition for laser cooling RaOH.

8.
Physiol Rep ; 11(19): e15837, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37813559

RESUMO

The peripartal period is marked by alterations in calcium metabolism to accommodate for embryonic skeletal mineralization and support bone development of offspring in early life, and serotonin plays a critical role in modulating peripartal bone remodeling. Selective serotonin reuptake inhibitors (SSRIs) are commonly used as first-line treatment for psychiatric illness during pregnancy and the postpartum period and considered safe for maternal use during this time frame. In order to evaluate the effect of peripartal alterations of the serotonergic system on maternal skeletal physiology, we treated dams with the SSRI fluoxetine during gestation only, lactation only, or during the entire peripartal period. Overall, we found a low dose of fluoxetine during gestation only had minimal impacts on maternal bone at weaning, but there were implications on maternal skeleton at weaning when dams were exposed during lactation only or during the entire peripartal period. We found that these effects were differential between female mice dosed lactationally or peripartally, and there were also impacts on maternal mammary gland at weaning in both of these groups. Though SSRIs are largely considered safe maternally during the peripartal period, this study raises the question whether safety of SSRIs, specifically fluoxetine, during the peripartal period should be reevaluated.


Assuntos
Fluoxetina , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Camundongos , Animais , Feminino , Humanos , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Lactação , Osso e Ossos/metabolismo , Desenvolvimento Ósseo , Efeitos Tardios da Exposição Pré-Natal/metabolismo
9.
ISME J ; 17(10): 1751-1764, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37558860

RESUMO

While genome sequencing has expanded our knowledge of symbiosis, role assignment within multi-species microbiomes remains challenging due to genomic redundancy and the uncertainties of in vivo impacts. We address such questions, here, for a specialized nitrogen (N) recycling microbiome of turtle ants, describing a new genus and species of gut symbiont-Ischyrobacter davidsoniae (Betaproteobacteria: Burkholderiales: Alcaligenaceae)-and its in vivo physiological context. A re-analysis of amplicon sequencing data, with precisely assigned Ischyrobacter reads, revealed a seemingly ubiquitous distribution across the turtle ant genus Cephalotes, suggesting ≥50 million years since domestication. Through new genome sequencing, we also show that divergent I. davidsoniae lineages are conserved in their uricolytic and urea-generating capacities. With phylogenetically refined definitions of Ischyrobacter and separately domesticated Burkholderiales symbionts, our FISH microscopy revealed a distinct niche for I. davidsoniae, with dense populations at the anterior ileum. Being positioned at the site of host N-waste delivery, in vivo metatranscriptomics and metabolomics further implicate I. davidsoniae within a symbiont-autonomous N-recycling pathway. While encoding much of this pathway, I. davidsoniae expressed only a subset of the requisite steps in mature adult workers, including the penultimate step deriving urea from allantoate. The remaining steps were expressed by other specialized gut symbionts. Collectively, this assemblage converts inosine, made from midgut symbionts, into urea and ammonia in the hindgut. With urea supporting host amino acid budgets and cuticle synthesis, and with the ancient nature of other active N-recyclers discovered here, I. davidsoniae emerges as a central player in a conserved and impactful, multipartite symbiosis.


Assuntos
Formigas , Nitrogênio , Animais , Formigas/fisiologia , Filogenia , Simbiose/genética , Ureia
10.
Oral Oncol ; 138: 106333, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36746098

RESUMO

OBJECTIVES: Examine the relationship between hospital volume and overall mortality in a surgical cohort of head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS & METHODS: A retrospective review of the NCDB was completed for adults with previously untreated HNSCC diagnosed between 2004 and 2016. Mean annual hospital volume was calculated using the number of head and neck cancer cases treated at a given facility divided by the number of years the facility reported to the NCDB. Facilities were separated into three categories based on their volume percentile, informed by inflection points from a natural cubic spline: Hospital Group 1 (<50%); Hospital Group 2 (50-90%); Hospital Group 3 (90%+). Cox proportional hazard models were used to examine the association between volume percentiles (continuous or categorical) with patient overall survival, adjusting for important patient and facility variables known to impact survival. RESULTS: Risk of death decreased by 2.97% for every 10% increase in facility percentile after adjusting for other risk factors. Patients treated at facilities in Hospital Group 1 had a 23.1% increase in risk of mortality (HR 1.231 [95% CI 1.12-1.35]) relative those at facilities in Hospital Group 3. No significant difference in mortality risk was found between Hospital Group 2 versus Hospital Group 3 (HR 1.031 [95% CI 0.97-1.10]). CONCLUSIONS: Survival of HNSCC patients is significantly improved when treated at facilities >50th percentile in annual hospital volume. This may support the regionalization of care to high volume head and neck centers with comprehensive facilities and supportive services to maximize patient outcomes.


Assuntos
Neoplasias de Cabeça e Pescoço , Hospitais , Adulto , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Retrospectivos , Modelos de Riscos Proporcionais
11.
Med Vet Entomol ; 37(2): 195-208, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36695750

RESUMO

There is an urgent need for continued research on the ecology of tick-borne diseases in Africa. Our objective was to provide a preliminary description of the ecology and epidemiology of tick species, tick-borne pathogens, and animal hosts in Zimbabwe, focusing efforts at Victoria Falls National Park, for a single season. We tested the hypothesis that tick surveillance and pathogen screening data can be used to model associations among ticks, hosts, and pathogens. We collected ticks from domesticated animals and wildlife in Zimbabwe and screened the ticks for the presence of Anaplasma and Ehrlichia bacteria. Nearly 30% of the screened ticks were PCR-positive; 89% of tick species were PCR-positive, and 88% of animal species carried at least one PCR-positive tick. We sequenced a subset of amplicons that were similar to three Anaplasma species and three Ehrlichia species. The odds of a tick being PCR-positive increased when many ticks were collected from the host or the tick was collected from a cow (domesticated animal). Tick species shared host species more often than expected. We demonstrate that ticks in northwestern Zimbabwe present a One Health problem for nearby wildlife and humans.


Assuntos
Rickettsia , Doenças Transmitidas por Carrapatos , Carrapatos , Bovinos , Feminino , Animais , Humanos , Anaplasma , Zimbábue/epidemiologia , Parques Recreativos , Estações do Ano , Ehrlichia , Animais Selvagens , Doenças Transmitidas por Carrapatos/microbiologia , Doenças Transmitidas por Carrapatos/veterinária
12.
Clin Podiatr Med Surg ; 40(1): 23-37, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36368846

RESUMO

Ankle syndesmosis injuries include isolated ligamentous rupture, as well as fractures with ligamentous injury. These injuries can significantly affect athletes in all sports, and lead to prolonged recovery and return to sport. Adequate evaluation and diagnosis of these injuries are imperative for treatment and return to play. Many can be treated nonoperatively, but operative treatment is indicated in fractures with syndesmosis disruption and ligamentous injuries with instability. Anatomic reduction and fixation of these injuries will allow functional rehab and return to sport.


Assuntos
Traumatismos do Tornozelo , Traumatismos em Atletas , Fraturas Ósseas , Humanos , Traumatismos do Tornozelo/diagnóstico , Traumatismos do Tornozelo/cirurgia , Articulação do Tornozelo/cirurgia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Fatores de Tempo , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/cirurgia
13.
J Palliat Med ; 26(5): 667-673, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36472545

RESUMO

Purpose: Primary palliative care (PPC) interventions are needed to address unmet symptom needs within standard oncology care. We designed an oncology nurse-led PPC intervention using shared care planning to facilitate patient engagement. This analysis examines the prevalence and severity of symptoms reported by patients and how symptoms were addressed on shared care plans (SCPs). Methods: Secondary analysis of a cluster randomized PPC intervention trial. Adult patients with metastatic solid tumors whose oncologist "would not be surprised if the patient died within a year" were included. Twenty-three oncology nurses received PPC training and conducted up to three monthly visits with patients. Symptom prevalence and severity were assessed before each visit using the Edmonton Symptom Assessment Scale (ESAS). Nurses collaboratively developed treatment strategies with patients, targeting the most bothersome symptoms for improvement. Results: Among 571 nurse-led PPC visits with 235 patients, the most prevalent and severe symptoms were tiredness (reported at 86% of visits; ESAS ≥4 in 55% of visits), low sense of wellbeing (78%; ESAS ≥4 in 38%), and poor appetite (69%; ESAS ≥4 in 42%). Moderately severe symptoms were addressed on SCPs ranging from 4% (drowsiness) to 35% (tiredness) of the time. Symptom management plans developed by PPC-trained oncology nurses primarily focused on nonpharmaceutical interventions (70%) compared with pharmaceutical interventions (30%). Conclusion: The symptoms that patients report most frequently and as most severe on SCPs were addressed less frequently than expected. Further research is needed to understand how PPC interventions can be designed to more effectively target and improve bothersome symptoms for patients with advanced cancer. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02712229.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Adulto , Humanos , Cuidados Paliativos , Papel do Profissional de Enfermagem , Neoplasias/patologia , Oncologia
14.
J Pers Disord ; 36(6): 717-730, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36454159

RESUMO

The current study sought to investigate the differential risk/protective factors of neuroticism and extraversion among individuals with only suicide ideation, those with a single suicide attempt, and those with multiple attempts. We hypothesized that extraversion would moderate the relation between neuroticism and suicide attempts (single and multiple) but not ideation. Patients in a private facility (N = 3343) completed measures assessing suicide history and general personality traits. Four moderation analyses were conducted with extraversion moderating the relationship between neuroticism and suicide ideation, single attempt (compared to zero attempts), and multiple attempts (compared to zero attempts and to single attempts). Extraversion moderated neuroticism only when comparing individuals with multiple suicide attempts to those with no attempts. Individuals who were low in both neuroticism and extraversion had higher levels of attempts than individuals with low neuroticism and high extraversion, highlighting the importance of considering biological predispositions as risk factors for suicide.


Assuntos
Extroversão Psicológica , Ideação Suicida , Humanos , Neuroticismo , Pacientes Internados , Tentativa de Suicídio
15.
J Vector Ecol ; 47(1): 29-37, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35366677

RESUMO

Prior research on baiting and feeding of wildlife found changes in habitat and the concentration of wildlife on a local scale (e.g., hundreds of meters). Since changes in habitat and host density affect ticks, feeding wildlife may lead to changes in tick and tick-borne disease ecology. We quantified the effect of feeding deer on ticks and tick-borne diseases at 79 pairs of sites with and without deer feeders during May-August of 2019 and 2020. We captured 0.4 fewer adult (p<0.05) and 1.2 fewer nymphal ticks (p=0.01) at feeder sites. This effect intensified over time with one fewer tick trapped at old feeders (≥5 years) compared to new feeders (<5 years, p<0.05). Greater daily wildlife visitation rates (p<0.001) may have allowed questing ticks to encounter hosts more readily. Most collected ticks were Amblyomma americanum (92.8%), a vector of Ehrlichia and Rickettsia pathogens, though prevalence of these pathogens did not differ (p>0.13) at a local scale. Supplemental deer feeding appears to influence ticks, possibly due to decreased tick habitat and increased wildlife use around feeders. Our findings indicate feeding does not lead to increased prevalence of Ehrlichia or Rickettsia bacteria within A. americanum locally.


Assuntos
Cervos , Rickettsia , Carrapatos , Animais , Ehrlichia , Mississippi
16.
Laryngoscope ; 132(10): 1953-1961, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-34989407

RESUMO

OBJECTIVES/HYPOTHESIS: We investigate the clinicopathologic and treatment factors associated with the use of postoperative radiation therapy (PORT) and its effect on overall survival (OS) for patients with oral cavity verrucous carcinoma (VC). STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective cohort study of the National Cancer Database (NCDB) from 2006 to 2015 was performed. Multivariable logistic regression was used to identify independent predictive factors associated with the use of PORT. Cox Regression survival and propensity score analyses were used to evaluate the effect of PORT on mortality. RESULTS: A total of 356 adult patients with primary oral cavity VC who underwent definitive surgical resection were identified. A total of 10.7% of patients underwent definitive surgical resection followed by PORT. Variables associated with PORT included distance to the hospital per 10 miles (adjusted odds ratio [aOR], 0.81 [95% confidence interval (CI), 0.70-0.95]) and stage III-IV disease (aOR, 12.13 and 23.92, respectively). Multivariable Cox regression survival analysis indicated no evidence of survival benefit in patients undergoing PORT compared to surgery alone (adjusted hazard ratio 1.50 [0.74-3.05], P = .23). Propensity score analysis also showed no OS benefit with the use of PORT (P = .41). CONCLUSIONS: Variables associated with the use of PORT on multivariable analysis included closer distance to hospital and stage III-IV disease. No clear survival benefit with PORT was identified on either multivariable survival analysis or propensity score analysis. These results suggest that surgery alone with negative margins may be the optimal treatment for patients with oral cavity VC. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1953-1961, 2022.


Assuntos
Carcinoma Verrucoso , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Adulto , Carcinoma Verrucoso/radioterapia , Carcinoma Verrucoso/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/radioterapia , Neoplasias Bucais/cirurgia , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
17.
Toxics ; 10(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35051053

RESUMO

Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressant used by pregnant women; however, they have been associated with adverse pregnancy outcomes and perinatal morbidity in pregnant women and animal models. We investigated the effects of two SSRI, fluoxetine and sertraline, on pregnancy and neonatal outcomes in mice. Wild-type mice were treated daily with low and high doses of fluoxetine (2 and 20 mg/kg) and sertraline (10 and 20 mg/kg) from the day of detection of a vaginal plug until the end of lactation (21 days postpartum). Pregnancy rate was decreased only in the high dose of fluoxetine group. Maternal weight gain was reduced in the groups receiving the high dose of each drug. Number of pups born was decreased in the high dose of fluoxetine and low and high doses of sertraline while the number of pups weaned was decreased in all SSRI-treated groups corresponding to increased neonatal mortality in all SSRI-treated groups. In conclusion, there was a dose-dependent effect of SSRI on pregnancy and neonatal outcomes in a non-depressed mouse model. However, the distinct placental transfer of each drug suggests that the effects of SSRI on pup mortality may be mediated by SSRI-induced placental insufficiency rather than a direct toxic effect on neonatal development and mortality.

18.
Elife ; 102021 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-34913435

RESUMO

Neural activity has been implicated in the motility and outgrowth of glial cell processes throughout the central nervous system. Here, we explore this phenomenon in Müller glia, which are specialized radial astroglia that are the predominant glial type of the vertebrate retina. Müller glia extend fine filopodia-like processes into retinal synaptic layers, in similar fashion to brain astrocytes and radial glia that exhibit perisynaptic processes. Using two-photon volumetric imaging, we found that during the second postnatal week, Müller glial processes were highly dynamic, with rapid extensions and retractions that were mediated by cytoskeletal rearrangements. During this same stage of development, retinal waves led to increases in cytosolic calcium within Müller glial lateral processes and stalks. These regions comprised distinct calcium compartments, distinguished by variable participation in waves, timing, and sensitivity to an M1 muscarinic acetylcholine receptor antagonist. However, we found that motility of lateral processes was unaffected by the presence of pharmacological agents that enhanced or blocked wave-associated calcium transients. Finally, we found that mice lacking normal cholinergic waves in the first postnatal week also exhibited normal Müller glial process morphology. Hence, outgrowth of Müller glial lateral processes into synaptic layers is determined by factors that are independent of neuronal activity.


When it comes to studying the nervous system, neurons often steal the limelight; yet, they can only work properly thanks to an ensemble cast of cell types whose roles are only just emerging. For example, 'glial cells' ­ their name derives from the Greek word for glue ­ were once thought to play only a passive, supporting function in nervous tissues. Now, growing evidence shows that they are, in fact, integrated into neural circuits: their activity is influenced by neurons, and, in turn, they help neurons to function properly. The role of glial cells is becoming clear in the retina, the thin, light-sensitive layer that lines the back of the eye and relays visual information to the brain. There, beautifully intricate Müller glial cells display fine protrusions (or 'processes') that intermingle with synapses, the busy space between neurons where chemical messengers are exchanged. These messengers can act on Müller cells, triggering cascades of molecular events that may influence the structure and function of glia. This is of particular interest during development: as Müller cells mature, they are exposed to chemicals released by more fully formed retinal neurons. Tworig et al. explored how neuronal messengers can influence the way Müller cells grow their processes. To do so, they tracked mouse retinal glial cells 'live' during development, showing that they were growing fine, highly dynamic processes in a region rich in synapses just as neurons and glia increased their communication. However, using drugs to disrupt this messaging for a short period did not seem to impact how the processes grew. Extending the blockade over a longer timeframe also did not change the way Müller cells developed, with the cells still acquiring their characteristic elaborate process networks. Taken together, these results suggest that the structural maturation of Müller glial cells is not impacted by neuronal signaling, giving a more refined understanding of how glia form in the retina and potentially in the brain.


Assuntos
Cálcio/metabolismo , Células Ependimogliais/fisiologia , Transmissão Sináptica , Animais , Cálcio/análise , Fenômenos Fisiológicos Celulares , Citosol/química , Citosol/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Retina/citologia , Retina/crescimento & desenvolvimento
19.
J Med Entomol ; 58(6): 2514-2518, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-34197609

RESUMO

Haemaphysalis longicornis Neumann (Asian longhorned tick) is an exotic and invasive tick species presenting a health and economic threat to the United States (U.S.) cattle industry due to its ability to transmit pathogens and infest hosts in large numbers. The objective of this study was to evaluate available products at causing H. longicornis mortality in a laboratory bioassay. The efficacy of products was evaluated at label rates using H. longicornis nymphs collected from a cattle farm in eastern Tennessee in two different bioassays (spray or dip) against untreated controls. After exposure, ticks were transferred to clean petri dishes and checked for mortality at 0, 1, 2, 3, 4, 21, 24, and 48 h post exposure. No mortality occurred in the untreated controls, whereas all treated ticks were dead within 24 h of exposure (P < 0.0001). These findings support the hypothesis that currently available spray and pour-on products are effective at causing H. longicornis mortality. We conclude that these acaricides can be used as a component to prevent H. longicornis dispersal and for control in the U.S.


Assuntos
Acaricidas , Espécies Introduzidas , Ixodidae , Controle de Ácaros e Carrapatos , Animais , Ixodidae/crescimento & desenvolvimento , Ninfa/crescimento & desenvolvimento , Tennessee , Controle de Ácaros e Carrapatos/instrumentação
20.
J Med Entomol ; 58(6): 2040-2046, 2021 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-33899103

RESUMO

The common bed bug (Cimex lectularius L.) is a known pest and an obligate blood-feeding ectoparasite. Bed bugs can feed on warm-blooded animals including humans, bats, poultry, and rabbits, but no research has investigated the use of companion animals (canines and/or felines) as a blood source. This study investigates how long known host DNA could be detected in a bed bug and the prevalence of bed bugs feeding on companion animals. Laboratory-reared bed bugs were fed host blood to determine how long DNA of human, feline, canine, and rabbit blood could be detected up to 21 d postfeeding. Additionally, 228 bed bugs were collected from 12 apartments with pets (6: canine, 5: feline, and 1: canine and feline), characterized as engorged or unengorged, and then screened with host-specific primers to identify the bloodmeal. Host meals of human, rabbit, feline, and canine blood were detected up to 21 d after feeding laboratory strains. All bed bugs died after feeding on the canine blood, but DNA could be detected up to 21 d post feeding/death. Of the field-collected bed bugs analyzed, human DNA was amplified in 158 (69.3%) bed bugs, canine DNA amplified in 7 bed bugs (3.1%), and feline DNA amplified in 1 bed bug (0.4%). Results of this study suggest that bed bugs predominately feed on humans and rarely feed on companion animals when they cohabitate in low-income, high-rise apartments. Additionally, results from this study warrant future investigations into host use by bed bugs in different housing structures and socioeconomic environments.


Assuntos
Percevejos-de-Cama/fisiologia , Doenças do Gato/parasitologia , Doenças do Cão/parasitologia , Ectoparasitoses/veterinária , Habitação/estatística & dados numéricos , Animais , Gatos , Cães , Ectoparasitoses/parasitologia , Comportamento Alimentar , Fatores Socioeconômicos , Tennessee
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