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2.
Artigo em Inglês | MEDLINE | ID: mdl-38403271

RESUMO

BACKGROUND: There is a lack of consensus on the optimal triage pathway for emergency department (ED) patients with mandibular fractures. It remains unclear if patient insurance payers predict hospital admission given potentially competing logistical and health system incentives. PURPOSE: To generate nationally representative estimates of the frequency of hospital admission and its association with primary insurance payers for ED patients with mandible fractures. METHODS: This retrospective cohort study used the 2018 Nationwide Emergency Department Sample, the largest all-payer database in the United States, to identify patients with mandible fractures. The database includes a stratified sample with discharge weights to generate nationally representative estimates. Patients with other facial fractures and/or concomitant injuries that independently warranted admission were excluded. PREDICTOR: The primary predictor variable was primary payer (public, private, self-pay, and other/no charge). OUTCOME VARIABLE: The primary outcome variable was hospital admission (yes/no). COVARIATES: Covariates included patient-, medical/injury-, and hospital-related variables. ANALYSES: Descriptive statistics, along with bivariate and multivariate logistic regression with Bonferroni correction, were used to produce national estimates and identify predictors of admission. P < .01 was considered significant. RESULTS: The cohort included 27,238 weighted encounters involving isolated mandible fractures, of which 5,345(20%) were admitted. The payers for admitted patients were 46% public, 25% private, 22% self-pay, and 7% no charge/other. In bivariate analyses, public insurance was associated with a higher likelihood of admission than private insurance (RR 1.24, 95% CI 1.06 to 1.45), though there was no association in the multivariate model (OR 1.03, 95% CI 0.83 to 1.28). In multivariate analysis, higher Charlson Comorbidity Index (OR 1.32, 95% CI 1.18 to 1.48), alcohol-related disorder (OR 3.47, 95% CI 2.74 to 4.39), substance-related disorder (OR 1.43, 95% CI 1.20 to 1.71), and more mandible fractures (OR 3.08, 95% CI 2.65 to 3.59) were associated with admission. Compared to body fractures, subcondylar (OR 3.83, 95% CI 2.39 to 6.14), angle (OR 3.53, 95% CI 2.84 to 6.09), and symphysis (OR 4.14, 95% CI 2.84 to 6.09) fractures had higher odds of admission. Finally, level I (OR 4.11, 95% CI 2.41 to 6.98) and level II (OR 3.16, 95% CI 1.85 to 5.39) trauma centers had higher odds of admission. CONCLUSIONS: In 2018, 20% of ED patients with isolated mandible fractures were admitted. Several patient and hospital characteristics were predictors of admission. Insurance status was not associated with admission.

3.
J Oral Maxillofac Surg ; 82(3): 332-340, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38199239

RESUMO

BACKGROUND: Advanced stage osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are challenging disease entities requiring multimodal therapy including surgical resection. However, risk factors associated with infection recurrence are poorly understood. PURPOSE: The purpose of this study was to identify risk factors associated with infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study including patients who underwent segmental mandibulectomy for management of ORN or MRONJ between 2016 and 2021 at the authors' institution. Subjects who did not have margin viability data were excluded. PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor variable was viability of resection margins on histopathologic analysis (viable or nonviable). Secondarily, other risk factors categorized as demographic (age, sex, race), medical (comorbidities), and perioperative (reconstructive modality, antibiotic duration, microbiological growth) were evaluated. MAIN OUTCOME VARIABLE: The primary outcome variable was time to infection recurrence defined as time from surgical resection to clinical diagnosis of a fistula tract, abscess, or persistent inflammatory symptoms necessitating surgical intervention. COVARIATES: Not applicable. ANALYSES: Descriptive and bivariate statistics were used to identify associations between risk factors and time to infection recurrence. A significance level of P ≤ .05 was considered significant. RESULTS: The cohort consisted of 57 subjects with a mean age of 63.3 ± 10.0 years (71.9% Male, 75.4% White) treated for ORN (47.4%) or MRONJ (52.6%). A total of 19/57 (33%) subjects developed a recurrence of infection with 1 and 2 year survival of 75.8 and 66.2%, respectively. Nonviable resection margins were associated with earlier time to infection recurrence (P ≤ .001, hazard ratio (HR) = 11.9, 95% confidence interval (CI) = 3.84 to 36.7) as was younger age (P = .005, HR = 0.921, 95% CI = 0.869 to 0.976) and atypical pathogen growth on culture (P = .002, HR = 8.58, 95% CI = 2.24 to 32.8). CONCLUSIONS AND RELEVANCE: Histopathologic margin viability was associated with earlier time to infection recurrence following resection of advanced stage ORN or MRONJ of the mandible. Additional studies are needed to identify interventions that may improve outcomes in this demographic.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Osteonecrose , Osteorradionecrose , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Estudos Retrospectivos , Margens de Excisão , Osteorradionecrose/cirurgia , Mandíbula/cirurgia , Fatores de Risco , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico
4.
bioRxiv ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38168186

RESUMO

Chimeric antigen receptor (CAR) T cells express antigen-specific synthetic receptors, which upon binding to cancer cells, elicit T cell anti-tumor responses. CAR T cell therapy has enjoyed success in the clinic for hematological cancer indications, giving rise to decade-long remissions in some cases. However, CAR T therapy for patients with solid tumors has not seen similar success. Solid tumors constitute 90% of adult human cancers, representing an enormous unmet clinical need. Current approaches do not solve the central problem of limited ability of therapeutic cells to migrate through the stromal matrix. We discover that T cells at low and high density display low- and high-migration phenotypes, respectively. The highly migratory phenotype is mediated by a paracrine pathway from a group of self-produced cytokines that include IL5, TNFα, IFNγ, and IL8. We exploit this finding to "lock-in" a highly migratory phenotype by developing and expressing receptors, which we call velocity receptors (VRs). VRs target these cytokines and signal through these cytokines' cognate receptors to increase T cell motility and infiltrate lung, ovarian, and pancreatic tumors in large numbers and at doses for which control CAR T cells remain confined to the tumor periphery. In contrast to CAR therapy alone, VR-CAR T cells significantly attenuate tumor growth and extend overall survival. This work suggests that approaches to the design of immune cell receptors that focus on migration signaling will help current and future CAR cellular therapies to infiltrate deep into solid tumors.

5.
Microbiol Resour Announc ; 13(2): e0102823, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38179909

RESUMO

Halomonas sp. SSL-5 is a Mn(II)-oxidizing, perchlorate-tolerant halophilic bacterium isolated from an Australian hypersaline lake. The genome sequence contains 27 contigs, and the genome is 3.4 Mb with a GC content of 67.2%. The sequence provides information for future studies of Mn(II) oxidation and perchlorate resistance under halophilic conditions.

6.
Head Neck ; 46(4): 797-807, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38193600

RESUMO

BACKGROUND: The relationship between hardware colonization, latent hardware complications, and hardware removal remains unclear following osteocutaneous free flap reconstruction of the jaws. METHODS: Retrospective cohort study of all patients undergoing free flap reconstruction of the maxilla or mandible from 2016 to 2021. RESULTS: A total of 240 subjects were included. Hardware colonization was associated with latent hardware complication in bivariate (p ≤ 0.001) and multivariate analysis (p ≤ 0.001). Time to latent hardware complication was 6.87 months earlier in colonized subjects (p ≤ 0.001). Of the 35 subjects undergoing hardware removal, 25 initiated but failed conservative therapy, and resolution of symptoms was achieved in 24 subjects after one operative intervention and 33 subjects after repeat intervention if indicated. CONCLUSIONS: Hardware colonization increases the risk and onset of latent hardware complication. Prompt hardware removal may improve outcomes by leading to faster resolution of symptoms without the burden and cost of conservative therapies.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Humanos , Retalhos de Tecido Biológico/efeitos adversos , Retalhos de Tecido Biológico/cirurgia , Estudos Retrospectivos , Procedimentos de Cirurgia Plástica/efeitos adversos , Mandíbula/cirurgia , Cabeça/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia
7.
J Oral Maxillofac Surg ; 81(11): 1422-1434, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37678417

RESUMO

BACKGROUND: Patients with head and neck cancer are at increased risk of malnutrition due to tumor burden and surgical morbidity. PURPOSE: The purpose of this study was to evaluate the association between preoperative serum albumin and 30-day adverse outcomes in patients undergoing head and neck cancer surgery. STUDY DESIGN, SETTING, SAMPLE: This was a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program database. Patients undergoing an ablative head and neck cancer procedure were included. Patients who had an unclear tumor location based on coding or missing outcome data were excluded. PREDICTOR VARIABLE: The primary predictor variable was preoperative albumin categorized as low (<3.4 g/dL), intermediate (3.4 to 3.9 g/dL), or high (>3.9 g/dL). OUTCOME VARIABLE: The primary outcome variable was intensive care unit (ICU)-level complications scored using the Clavien-Dindo classification system. This is a tool used to grade surgical complications, with grade IV and V complications defined as requiring ICU-level care. COVARIATES: Covariates were demographic (age, sex, body mass index), medical (smoking, functional status, weight loss), and perioperative (concurrent procedures, tumor location, reconstructive modality). ANALYSES: Descriptive, bivariate, and multiple logistic regression with bootstrap resampling statistics were used to evaluate the association between albumin and adverse outcomes. A significance level of P ≤ .05 was significant. RESULTS: A total of 4,491 subjects met inclusion criteria and had a documented albumin. There were 435 subjects with low albumin levels, 1,305 with intermediate levels, and 2,751 with high levels. In bivariate analysis, low albumin levels were associated with an increased risk of ICU-level complications, any complication, extended length of stay, and adverse discharge disposition (all P ≤ .001), while high levels were protective (all P ≤ .001). In bootstrapped multivariate analysis using intermediate albumin as the reference group and adjusting for demographics, tumor location, and reconstructive modality among others, low albumin levels were an independent predictor of ICU-level complications (P = .008, odds ratio, 1.64; 95% confidence interval, 1.14 to 2.40), while high levels were protective (P = .014, odds ratio, 0.689; 95% confidence interval, 0.521 to 0.923). CONCLUSIONS: Preoperative serum albumin was an independent predictor of adverse outcomes following ablative head and neck cancer procedures.


Assuntos
Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Humanos , Albumina Sérica , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Neoplasias de Cabeça e Pescoço/cirurgia , Fatores de Risco
8.
J Immunol ; 211(8): 1240-1248, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37682538

RESUMO

B cell-targeted therapies are effective for treating multiple different kidney diseases in humans and also protect mice from Adriamycin nephropathy. Because glomerular IgM is frequently seen in both humans and mice with "nonimmune" forms of glomerular disease, we hypothesized that natural IgM binds to epitopes displayed in the injured glomerulus, exacerbating injury. To test this hypothesis, we induced Adriamycin nephropathy in BALB/C mice that cannot secrete soluble IgM (sIgM-/- mice) and compared them with BALB/C controls. Contrary to our prediction, we found that female sIgM-/- mice developed higher mortality and more severe kidney injury after injection of Adriamycin. The absence of soluble IgM did not reduce glomerular complement activation, and IgG was seen deposited within the injured glomeruli. Furthermore, we discovered that female sIgM-/- mice have higher levels of anti-cardiolipin IgG, and that IgG from these mice binds to epitopes in the injured kidney. These findings indicate that natural IgM may prevent generation of autoreactive IgG. Circulating levels of anti-cardiolipin IgG decreased after induction of kidney injury in female mice, consistent with deposition of the Abs in injured tissues. Better understanding of the mechanisms by which the immune system modulates and amplifies kidney injury may enable the development of targeted therapies to slow kidney disease progression.


Assuntos
Imunoglobulina M , Nefropatias , Animais , Feminino , Camundongos , Doxorrubicina , Epitopos , Imunoglobulina G , Camundongos Endogâmicos BALB C
9.
Cureus ; 15(8): e43983, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37746480

RESUMO

INTRODUCTION: Transgender and gender diverse (TGD) individuals, comprised of those whose gender identity does not correspond with the sex they were assigned at birth, represent approximately 1.4 million people in the U.S., with a higher prevalence among those 18-24 years old. TGD individuals experience high levels of intimate partner violence (IPV), which leads to disproportionately negative mental and physical health outcomes for this population. As a result, there is a resounding need to connect TGD populations to health-promoting services, supports and resources. Med-Peds and Family Medicine clinics may be particularly well-positioned to support these efforts due to physicians' focus on transitional-aged youth and young adults under 30. METHODS: The current manuscript reports on processes and outcomes related to a quality improvement (QI) initiative that aimed to test the feasibility and acceptability of implementing IPV screening within both a Med-Peds and a Family Medicine specialty clinic serving TGD populations in Los Angeles, CA. This QI initiative included screeners that capture IPV in cisgender/non-TGD populations (Humiliation, Afraid, Rape, Kick [HARK]) as well as in TGD populations specifically (IPV-T). We utilized a mixed-methods approach to both quantify and qualify responses to existing IPV screening as well as informal feedback from clinic "champions" in each clinic. RESULTS: Quantitative and qualitative findings from this QI initiative, featuring both general and TGD-specific IPV screening measures with 140 TGD individuals, elucidated several important processes that can support effective IPV screening and referral to supports and services. These include the importance of interdisciplinary teams, the utility of an iterative approach to screener roll-out, and the essential role of solidifying a referral process in these efforts. This project additionally shed light on the potential utility and challenges of implementing both general and TGD-specific IPV screening measures. Our pilot test did not support the necessity of a TGD-specific IPV screener for identifying and responding to IPV in this population, yet additional data is critical to generate more conclusive recommendations. CONCLUSION: We recommend larger-scale data collection efforts to evaluate the utility of integrating general and TGD-specific screeners into clinic workflows to ensure optimal health promotion for the TGD population in Med-Peds and Family Medicine clinics.

10.
Sci Rep ; 13(1): 12536, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37532755

RESUMO

This study improves the understanding of circulation patterns associated with regional temperature trends by characterizing boreal summer temperature variability patterns in North America using rotated S-mode principal component analysis. We analyzed gridded observational 2-m temperature datasets and the ERA5 reanalysis temperature dataset to examine the climate patterns associated with long-term trends and inter-annual variability of temperature variability patterns in North America. Our analysis revealed significant trends among some classified temperature variability patterns from 1979 to 2022 summers, with inter-annual amplitudes (i.e., a departure from the mean state) signaling toward the warm regime. The anticyclonic circulation anomaly over the temperature coherent regions associated with Greenland/northeastern Canada, and Alaska, respectively, is linked to an increase in warm air advection and above-average temperatures, while cyclonic circulation over the northeast Pacific coast enhanced warm air advection and temperature increases in the coherent region comprising the northwestern portion of North America. The increase in global mean land and ocean temperatures is strongly associated with the long-term increase in the amplitude of atmospheric circulations associated with warm regimes in parts of North America. At the interannual time scale, temperature increase over Greenland/northeastern Canada is strongly associated with the negative phase of the Arctic Oscillation. These findings highlight the modulating effects of global temperature increase and warming of the western tropical Pacific Ocean on the increasing amplitude of circulations associated with warm regimes in North America. Our results further indicate that the enhancement of anticyclonic circulations over the Arctic contributes to nearly 68% of the observed reduction in sea ice extent.

11.
Biomedicines ; 11(7)2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37509694

RESUMO

The continuing transmission of coronavirus disease 2019 (COVID-19) remains a world-wide 21st-century public health emergency of concern. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused greater than 600 million cases of COVID-19 and over 6 million deaths globally. COVID-19 continues to be a highly transmissible disease despite efforts by public health officials and healthcare providers to manage and control the disease. Variants identified in selected worldwide epicenters add to the complexity of vaccine efficacy, overage, and antibody titer maintenance and bioactivity. The identification of the SARS-CoV-2 variants is described with respect to evading protective efficacy of COVID-19 vaccines and breakthrough infections. Vaccines and other therapeutics have prevented millions of SARS-CoV-2 infections and thousands of deaths in the United States. We explore aspects of the immune response in a condensed discussion to understand B and T cell lymphocyte regulatory mechanisms and antibody effectiveness and senescence. Finally, COVID-19 therapies including Paxlovid, Remdisivir, Molnupiravir and convalescent plasma in non-hospitalized patients are presented with limitations for identification, collection, and distribution to infected patients.

13.
Adm Policy Ment Health ; 50(5): 773-780, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37266799

RESUMO

To improve the dissemination and actionability of mental health research, many mental health professionals have developed online informational resources to increase the general public's awareness of mental health difficulties and available treatments. Yet, limited information exists on the quality and scope of these resources. This study aimed to explore the scope and quantity of online, free, evidence-based mental health resources. Fifty-two mental health professionals nominated 178 resources, which predominantly consisted of homepages and links to more information. When reviewing the original nominations, our team identified an additional 290 resources (e.g., fact sheets linked from a nominated homepage). Of the 468 total nominated resources, 72 were screened out due to not meeting the inclusion criteria of being free (inter-screener reliability = 95%), evidence-based (inter-screener reliability = 94%), and online (inter-screener reliability = 96%). Nominated resources most commonly covered anxiety and obsessive-compulsive disorder (n = 67) and suicide (n = 60). Resources providing information about the mental health problem were most common (n = 210) and resources providing information about immediate help (e.g., hotline) were least common (n = 57). Our findings indicate many free, online, evidence-based resources are available and raise questions of whether efforts to disseminate mental health research are recreating the issue of information overload. Other considerations and future directions for improving the utilization and synthesizing of available resources are discussed.


Assuntos
Saúde Mental , Suicídio , Humanos , Reprodutibilidade dos Testes , Transtornos de Ansiedade , Recursos em Saúde
14.
Mol Cell ; 83(10): 1623-1639.e8, 2023 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-37164018

RESUMO

The HUSH complex recognizes and silences foreign DNA such as viruses, transposons, and transgenes without prior exposure to its targets. Here, we show that endogenous targets of the HUSH complex fall into two distinct classes based on the presence or absence of H3K9me3. These classes are further distinguished by their transposon content and differential response to the loss of HUSH. A de novo genomic rearrangement at the Sox2 locus induces a switch from H3K9me3-independent to H3K9me3-associated HUSH targeting, resulting in silencing. We further demonstrate that HUSH interacts with the termination factor WDR82 and-via its component MPP8-with nascent RNA. HUSH accumulates at sites of high RNAPII occupancy including long exons and transcription termination sites in a manner dependent on WDR82 and CPSF. Together, our results uncover the functional diversity of HUSH targets and show that this vertebrate-specific complex exploits evolutionarily ancient transcription termination machinery for co-transcriptional chromatin targeting and genome surveillance.


Assuntos
Inativação Gênica , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Transcrição Gênica , Genoma/genética , RNA
15.
MicroPubl Biol ; 20232023.
Artigo em Inglês | MEDLINE | ID: mdl-37012989

RESUMO

In rich medium, W303 Saccharomyces cerevisiae begins to accumulate in G1 an hour before it exhausts the available glucose. It undergoes one more asymmetrical cell division, then stops dividing in G1. In contrast, BY4741, stops dividing four hours before glucose exhaustion, at one-fourth the cell density achieved by W303. There is no asymmetrical cell division and only 50% of the cells arrest in G1. We conclude that BY4741 growth is not limited by glucose and they do not go through the stereotypical events carried out by other strains as they enter quiescence from rich medium. In W303, the timing of glucose limitation and the transition to quiescence is correlated with the rate of biomass accumulation and cell doubling time.

16.
J Oral Maxillofac Surg ; 81(7): 831-837, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37004839

RESUMO

PURPOSE: Oral-maxillofacial surgeons (OMSs) are frequent prescribers of opioid analgesics. It remains unclear if prescription patterns differ for urban versus rural patients, given potential differences in access to and delivery of care. This study aimed to characterize urban-rural differences in opioid analgesic prescriptions to patients in Massachusetts by OMSs from 2011 to 2021. METHODS: This retrospective cohort study used the Massachusetts Prescription Monitoring Program database to identify Schedule II and III opioid prescriptions by providers with specialty of oral and maxillofacial surgery from 2011 to 2021. The primary predictor variable was patient geography (urban/rural) and secondary predictor was year (2011-2021). The primary outcome variable was milligram morphine equivalent (MME) per prescription. Secondary outcome variables were days' supply per prescription and number of prescriptions received per patient. Descriptive and linear regression statistics were performed to analyze differences in prescriptions to urban and rural patients each year and throughout the study period. RESULTS: The study data, which includes OMS opioid prescriptions (n = 1,057,412) in Massachusetts from 2011 to 2021, ranged annually between 63,678 and 116,000 prescriptions to between 58,000 and 100,000 unique patients. The cohorts each year ranged between 48 and 56% female with mean ages between 37 and 44 years. There were no differences in the mean number of patients per provider in urban and rural populations in any year. The study sample had a large majority of urban patients (>98%). MME per prescription, days' supply per prescription, and prescriptions received per patient were all generally similar between urban and rural patients each year, with the largest MME per prescription difference in 2019 (87.3 for rural to 73.9 for urban patients, P < .01). From 2011 to 2021, all patients had a steady decrease in MME per prescription (ß = -6.64, 95% confidence interval: -6.81, -6.48; R2 = 0.39) and day's supply per prescription (ß = -0.1, 95% confidence interval: -0.1, -0.09; R2 = 0.37). CONCLUSION: In Massachusetts, there were similar opioid prescribing patterns by oral and maxillofacial surgeons to urban and rural patients from 2011 to 2021. There has also been a steady decrease in the duration and total dosage of opioid prescriptions to all patients. These results are consistent with multiple statewide policies over the last several years aimed at curbing opioid overprescribing.


Assuntos
Analgésicos Opioides , Cirurgiões Bucomaxilofaciais , Humanos , Feminino , Adulto , Masculino , Analgésicos Opioides/uso terapêutico , População Rural , Estudos Retrospectivos , Padrões de Prática Odontológica , Massachusetts , Prescrições , Padrões de Prática Médica , Prescrições de Medicamentos
18.
Clin Transl Sci ; 16(4): 662-672, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36760155

RESUMO

Although major advancements have been made in the therapeutics for people with cystic fibrosis (PwCF), many still require the use of multiple medications to manage acute exacerbations of disease and maintain health. Iterative trial and error processes of pharmacotherapeutic management can be optimized by assessing and incorporating pharmacogenetics. For 82 PwCF, we reviewed 2 years of medication use and response history and interrogated metabolizer status for common pharmacogenes, revealing 3336 medication exposure events (MEEs) to 286 unique medications. As expected, the more frequent MEEs were those commonly used to treat cystic fibrosis (CF), such as antibiotics and respiratory medications. Antibiotics also comprised 56.7% of the undesirable drug responses. The impact of gene variants on drug responses was assessed using Pharmacogenomics Knowledgebase (PharmGKB) and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Thirty-three (11.5%) medications have strong evidence of genetic influence on response as evidenced by gene-based dosing guidelines. 110 (38.5%) unique medications had at least one association with a very important pharmacogene, whereas 143 (50%) were associated with at least one clinical or variant annotation. Over 97% of participants had at least one actionable genotype. Eleven (13.4%) patients with an actionable genotype, taking the impacted medication, had an undesirable drug response described in the CPIC guidelines that could potentially have been mitigated with a priori knowledge of the genotype. PwCF take many medications for disease management, with frequent dose changes to elicit a desired clinical effect. As CF care evolves, implementing pharmacogenetics testing can improve efficiency and safety of prescribing practices using precision selection and dosing at medication initiation.


Assuntos
Antineoplásicos , Fibrose Cística , Humanos , Farmacogenética , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Prescrições de Medicamentos , Genótipo
19.
J Oral Maxillofac Surg ; 81(2): 172-183, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36403659

RESUMO

PURPOSE: Interfacility hospital transfer for isolated midfacial fractures is common but rarely clinically necessary. The purpose of this study was to generate nationally representative estimates regarding the incidence, risk factors, and cost of transfer for isolated midface fractures. METHODS: This was a retrospective cohort study using the Nationwide Emergency Department Sample 2018 to identify patients with isolated midface fractures. The primary predictor variable was hospital trauma center designation (Level I, Level II, Level III, and nontrauma center). The primary outcome variable was hospital transfer. Total emergency department (ED) charges were also assessed. Covariates were demographic, medical, injury-related, and hospital characteristics. Descriptive, bivariate, and multiple logistic regression statistics were used to evaluate the incidence and predictors of interfacility transfer. RESULTS: During the study period, there were 161,022 ED encounters with a midface fracture as primary diagnosis, of which 5,680 were transferred (3.53%). In an unadjusted analysis, evaluation at a nontrauma center, level III trauma center, nonteaching hospital, and numerous demographic, medical, and injury-related variables were associated with transfer (P ≤ .001). In the adjusted model, the strongest independent predictors for hospital transfer were evaluation at a nontrauma center (odds ratio [OR] = 16.2, 95% confidence interval [CI] = 13.6-19.4), level III trauma center (OR = 13.4, 95% CI = 11.1-16.1) or level II trauma center (OR = 3.25, 95% CI = 2.66-3.98), any Le Fort fracture (OR = 12.0, 95% CI = 10.4-14.0), orbital floor fracture (OR = 3.73, 95% CI = 3.48-4.00), history of cerebrovascular event (OR = 2.74, 95% CI = 2.18-3.45), and cervical spine injury (OR = 5.87, 95% CI = 4.79-7.20) (P ≤ .001). The average ED charge per encounter was $7,206 ± 9,294 for a total nationwide charge of approximately 1.16 billion dollars. Transferred subjects had total ED charges of $97 million, not including additional charges at the recipient hospital. CONCLUSION: Isolated midface fractures are transferred infrequently, but given the high incidence have substantial healthcare costs. Predictors of transfer were mixed rather than clustered within one variable type, although it is likely that transfers are driven in part by lack of access to maxillofacial specialists given the predominance of hospital covariates. Programs evaluating necessity of transfer and facilitating specialist evaluation in the outpatient setting may reduce healthcare expenditures for these injuries.


Assuntos
Serviço Hospitalar de Emergência , Centros de Traumatologia , Humanos , Estados Unidos/epidemiologia , Estudos Retrospectivos , Face , Ossos Faciais/lesões
20.
Front Cell Dev Biol ; 10: 989820, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172269

RESUMO

During mitosis, cells must spatiotemporally regulate gene expression programs to ensure accurate cellular division. Failures to properly regulate mitotic progression result in aneuploidy, a hallmark of cancer. Entry and exit from mitosis is largely controlled by waves of cyclin-dependent kinase (CDK) activity coupled to targeted protein degradation. The correct timing of CDK-based mitotic regulation is coordinated with the structure and function of microtubules. To determine whether mitotic gene expression is also regulated by the integrity of microtubules, we performed ribosome profiling and mRNA-sequencing in the presence and absence of microtubules in the budding yeast Saccharomyces cerevisiae. We discovered a coordinated translational and transcriptional repression of genes involved in cell wall biology processes when microtubules are disrupted. The genes targeted for repression in the absence of microtubules are enriched for downstream targets of a feed-forward pathway that controls cytokinesis and septum degradation and is regulated by the Cbk1 kinase, the Regulation of Ace2 Morphogenesis (RAM) pathway. We demonstrate that microtubule disruption leads to aberrant subcellular localization of Cbk1 in a manner that partially depends on the spindle position checkpoint. Furthermore, constitutive activation of the RAM pathway in the absence of microtubules leads to growth defects. Taken together, these results uncover a previously unknown link between microtubule function and the proper execution of mitotic gene expression programs to ensure that cell division does not occur prematurely.

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