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1.
Cell ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38876107

RESUMO

Vector-borne diseases are a leading cause of death worldwide and pose a substantial unmet medical need. Pathogens binding to host extracellular proteins (the "exoproteome") represents a crucial interface in the etiology of vector-borne disease. Here, we used bacterial selection to elucidate host-microbe interactions in high throughput (BASEHIT)-a technique enabling interrogation of microbial interactions with 3,324 human exoproteins-to profile the interactomes of 82 human-pathogen samples, including 30 strains of arthropod-borne pathogens and 8 strains of related non-vector-borne pathogens. The resulting atlas revealed 1,303 putative interactions, including hundreds of pairings with potential roles in pathogenesis, including cell invasion, tissue colonization, immune evasion, and host sensing. Subsequent functional investigations uncovered that Lyme disease spirochetes recognize epidermal growth factor as an environmental cue of transcriptional regulation and that conserved interactions between intracellular pathogens and thioredoxins facilitate cell invasion. In summary, this interactome atlas provides molecular-level insights into microbial pathogenesis and reveals potential host-directed targets for next-generation therapeutics.

2.
Head Neck ; 46(5): 1160-1167, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38494924

RESUMO

BACKGROUND: Fibula free flaps (FFF) are one of the most common bony flaps utilized. This paper describes a quality improvement project aimed at increasing early ambulation. METHODS: A review of FFF patients at an academic hospital was completed (2014-2023). In 2018, an institutional change to encourage early ambulation without placement of a boot was made. Changes in hospital disposition and physical therapy outcomes were evaluated. RESULTS: A total of 168 patients underwent FFF reconstruction. There was a statistically significant lower length of stay in Group 2 (early ambulation, no boot) (8.1 vs. 9.4; p = 0.04). A higher rate of discharge to a skilled nursing facility was noted in Group 1 (delayed ambulation with boot) (21.3% vs. 11.9%; p = 0.009). A higher proportion of patients in Group 2 demonstrated independence during bed mobility, transfers, and gait (p < 0.05). CONCLUSIONS: Early ambulation without boot placement after FFF is associated with decreased length of hospital stay, improved disposition to home and physical therapy outcomes.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Humanos , Alta do Paciente , Tempo de Internação , Deambulação Precoce , Estudos Retrospectivos
3.
J Behav Med ; 47(3): 405-421, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38418709

RESUMO

Loneliness may exacerbate poor health outcomes particularly among cancer survivors during the COVID-19 pandemic. Little is known about the risk factors of loneliness among cancer survivors. We evaluated the risk factors of loneliness in the context of COVID-19 pandemic-related prevention behaviors and lifestyle/psychosocial factors among cancer survivors. Cancer survivors (n = 1471) seen at Huntsman Cancer Institute completed a survey between August-September 2020 evaluating health behaviors, medical care, and psychosocial factors including loneliness during COVID-19 pandemic. Participants were classified into two groups: 'lonely' (sometimes, usually, or always felt lonely in past month) and 'non-lonely' (never or rarely felt lonely in past month). 33% of cancer survivors reported feeling lonely in the past month. Multivariable logistic regression showed female sex, not living with a spouse/partner, poor health status, COVID-19 pandemic-associated lifestyle factors including increased alcohol consumption and marijuana/CBD oil use, and psychosocial stressors such as disruptions in daily life, less social interaction, and higher perceived stress and financial stress were associated with feeling lonely as compared to being non-lonely (all p < 0.05). A significant proportion of participants reported loneliness, which is a serious health risk among vulnerable populations, particularly cancer survivors. Modifiable risk factors such as unhealthy lifestyle behaviors and psychosocial stress were associated with loneliness. These results highlight the need to screen for unhealthy lifestyle factors and psychosocial stressors to identify cancer survivors at increased risk of loneliness and to develop effective management strategies.


Assuntos
COVID-19 , Sobreviventes de Câncer , Neoplasias , Humanos , Feminino , Solidão/psicologia , Pandemias , Fatores de Risco , Comportamentos Relacionados com a Saúde
4.
Ann Otol Rhinol Laryngol ; 133(4): 441-448, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38321924

RESUMO

OBJECTIVE: Primary hyperparathyroidism (PHPT) affects approximately 0.86% of the population, with surgical resection as the treatment of choice. A 4D computed tomography (CT) is a highly effective tool in localizing parathyroid adenomas; however, there is currently no defined role for 4D CT when stratified against ultrasonography (USG) and nuclear medicine Technetium Sestamibi SPECT/CT (SES) imaging. STUDY DESIGN: Retrospective Study. SETTING: University Hospital. METHODS: All patients who underwent parathyroidectomy for PHPT between 2014 and 2019 at a single institution were reviewed. Patients who had a 4D CT were included. We compared outcomes of 4D CT as a second line imaging modality to those of USG and SES as first line modalities. An imaging algorithm was proposed based on these findings. RESULTS: There were 84 patients identified who had a 4D CT after unsuccessful first line imaging. A 4D CT localized parathyroid adenoma to the correct quadrant in 64% of cases, and to the correct laterality in 75% of cases. Obese patients had significantly lower rates of adenoma localization with USG (33.4%), compared to non-obese patients (67.5%; P = .006). In determining multigland disease the sensitivity of 4D CT was 86%, while the specificity was 87%. CONCLUSIONS: A 4D CT has impressive rates of accurate localization of parathyroid adenomas; however due to the radiation exposure involved, it should remain a second line imaging modality. PHPT patients should first be evaluated with USG, with 4D CT used if this is unsuccessful and patients are greater than 40 years old, have a high BMI, or are having revision surgery.


Assuntos
Hiperparatireoidismo Primário , Neoplasias das Paratireoides , Humanos , Adulto , Neoplasias das Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/cirurgia , Glândulas Paratireoides , Tomografia Computadorizada Quadridimensional/métodos , Hiperparatireoidismo Primário/diagnóstico por imagem , Hiperparatireoidismo Primário/cirurgia , Estudos Retrospectivos , Paratireoidectomia/métodos , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade
5.
J Am Mosq Control Assoc ; 40(1): 1-10, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38314881

RESUMO

While most research on West Nile virus (WNV) and its main vector, the Culex mosquito, has been conducted in laboratory or urban settings, studies with field-caught mosquitoes in rural areas, such as west-central Illinois, are lacking. The objective of this research was to investigate key abiotic factors using macroclimate data, including temperature, precipitation, and wind speed, to determine their influence on field-caught mosquito abundance in 4 rural counties in Illinois from 2014 to 2016. Additionally, the relationship between minimum infection rate (MIR) and thermal time was examined. Using gravid traps at 15 sites, Culex mosquitoes were collected twice a week. A total of 5,255 adult female Culex mosquitoes (Cx. pipiens, Cx. quinquefasciatus, and Cx. restuans) were collected in 2014; 9,138 in 2015; and 5,702 in 2016. Regression models were developed based on outcomes of relationships between field-caught mosquitoes and abiotic factors. Precipitation and thermal time had the most significant relationship with mosquito abundance (r2 = 0.993 and r2 = 0.993, respectively), while wind speed was less (r2 = 0.714). The greatest number of Culex and the highest annual MIR were observed in 2015, which was also the driest of the 3 sampling seasons. Mosquito abundance was observed to increase with warmer degree days and MIR was found to increase with abundance in mosquitoes. These models can be used for other mosquito surveillance and monitoring studies in various climate types and environments.


Assuntos
Culex , Culicidae , Febre do Nilo Ocidental , Animais , Feminino , Febre do Nilo Ocidental/epidemiologia , Temperatura , Vento , Mosquitos Vetores , Illinois/epidemiologia
6.
J Stud Alcohol Drugs ; 85(3): 381-388, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38206669

RESUMO

OBJECTIVE: This project aimed to characterize the relationship between physical pain experienced at time of entry to residential treatment for substance use disorders (SUDs) and the frequency of treatment dropout. We hypothesized that both endorsement of recent pain and higher magnitude of endorsed pain intensity would be associated with higher dropout rates. We further hypothesized that these effects would be exacerbated among patients with opioid use disorder (OUD). METHOD: Participants included 1,095 individuals in residential treatment for SUD. Data were collected within 24 hours of treatment entry. Analyses were conducted using logistic regression with dropout as the dependent variable. Dropout was operationally defined as leaving treatment against medical advice or being discharged from treatment because of use of substances. Pain (including endorsement and intensity) was the primary independent variable in all analyses. Analyses included demographic and affective covariates and included both main effects of OUD and interaction terms between OUD and pain. RESULTS: Pain endorsement was associated with greater frequency of dropout (odds ratio [OR] = 1.49, p = .04). Higher levels of pain intensity predicted increased rates of dropout (OR = 1.13, p < .01). In contrast with our hypothesis, no interactions between OUD and pain were observed. CONCLUSIONS: These results underscore the import of integrating pain monitoring and pain interventions as core components of treatment for SUD. Our findings are highly consistent with a growing literature recognizing the impact of pain across a constellation of important treatment outcomes and provide novel data strongly suggesting that pain predicts early cessation of treatment.


Assuntos
Transtornos Relacionados ao Uso de Opioides , Dor , Pacientes Desistentes do Tratamento , Transtornos Relacionados ao Uso de Substâncias , Humanos , Masculino , Feminino , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Adulto , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Transtornos Relacionados ao Uso de Opioides/reabilitação , Dor/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Pessoa de Meia-Idade , Tratamento Domiciliar/métodos
7.
J Addict Dis ; : 1-10, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37380371

RESUMO

Objectives: Chronic pain is both an important antecedent and consequence of substance use. Although evidence suggests healthcare professionals may be uniquely vulnerable to chronic pain, this vulnerability remains largely unexamined in the context of recovery from substance use disorders (SUDs). We characterized pain in a sample of treatment-seeking individuals, examined potential differences in pain trajectories between healthcare professionals and non-healthcare patients, and interrogated potential pain-related vulnerabilities in treatment outcomes between these groups. Methods: Patients with SUDs (n = 663; 251 women) completed questionnaires indexing pain intensity, craving, and abstinence self-efficacy (including self-efficacy in pain-related contexts). Assessments were conducted at treatment entry, 30 days, and discharge. Analyses included chi-square and longitudinal mixed models. Results: The proportion of healthcare and non-healthcare patients endorsing recent pain was equivalent (χ2=1.78, p=.18). Healthcare professionals reported lower pain intensity (p = 0.02) and higher abstinence self-efficacy (p < 0.001). Profession by pain interactions (ps <.040) revealed that among medical professionals, associations between pain and all three treatment outcomes of interest were more robust relative to the non-healthcare group. Conclusions: Results suggest that although healthcare professionals endorse similar rates of pain and lower average pain intensity, they may be uniquely vulnerable to pain-related disruptions in craving and abstinence self-efficacy.

8.
J Am Mosq Control Assoc ; 39(1): 1-11, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-37043607

RESUMO

A comprehensive surveillance of Aedes mosquitoes in west-central Illinois has not been conducted in recent years, resulting in incomplete distribution records for several Illinois counties. As of 2014, out of 102 Illinois counties, active populations of Ae. japonicus had been confirmed in 15 counties, and Ae. albopictus confirmed in 34 counties. The Miller laboratory at Western Illinois University (WIU) began the WIU Vector Biology Initiative (WIU-VBI) in 2014 to address the lack of mosquito surveillance in west-central Illinois. Through this effort, the presence of Ae. japonicus was confirmed for the 1st time in Fulton, Hancock, and Schuyler counties, IL, from 2014 to 2018. Actively breeding populations were confirmed in Cass, Fulton, McDonough, and Schuyler counties, IL. Additionally, Ae. albopictus was observed for the 1st time in Cass, Fulton, Hancock, McDonough, and Schuyler counties, IL, in 2016 and 2017, with active breeding populations in Cass and McDonough counties, IL.


Assuntos
Aedes , Animais , Humanos , Mosquitos Vetores , Illinois , Distribuição Animal
9.
Am J Addict ; 32(3): 254-262, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36566359

RESUMO

BACKGROUND AND OBJECTIVES: Adverse events during childhood increase the risk for the development of substance use disorders (SUDs). This study examined the association between adverse childhood experiences (ACEs) and SUD treatment response. METHODS: This cohort analysis included data from longitudinal clinical assessments extracted from the records of 438 consenting individuals undergoing SUD treatment (63% male; 88.8% White). Mixed effects models evaluated the relationship between scores on the ACE questionnaire and indicators of treatment response (i.e., alcohol and drug abstinence self-efficacy; symptoms of depression, anxiety, and posttraumatic stress disorder) for individuals with alcohol-related (n = 332) and other drug-related (n = 275) diagnoses, with some participants included in both groups. RESULTS: Treatment response varied as a function of ACEs, with the magnitude of differences varying across time in treatment. Relative to those with no ACE history, those who experienced ≥2 ACEs reported worse depression, anxiety, PTSD symptoms, and alcohol/drug abstinence self-efficacy at baseline, with many differences remaining at the 30-day assessment. All differences abated by discharge, with the exception of PTSD symptoms among those in the drug use group with a history of ≥4 ACEs. Male gender and older age were generally associated with lower symptomology and higher abstinence self-efficacy. DISCUSSION AND CONCLUSIONS: Assessing ACE history early in SUD treatment may improve treatment planning and prognosis. Future studies should evaluate the role of trauma-informed programming and individual interventions to improve treatment response. SCIENTIFIC SIGNIFICANCE: This study demonstrates the association between adverse childhood experiences and symptom severity among patients across participation in SUD treatment.


Assuntos
Experiências Adversas da Infância , Transtornos de Estresse Pós-Traumáticos , Transtornos Relacionados ao Uso de Substâncias , Adulto , Humanos , Masculino , Feminino , Transtornos Relacionados ao Uso de Substâncias/terapia , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Ansiedade , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inquéritos e Questionários
10.
J Natl Compr Canc Netw ; 20(8): 925-951, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35948029

RESUMO

Differentiated thyroid carcinomas is associated with an excellent prognosis. The treatment of choice for differentiated thyroid carcinoma is surgery, followed by radioactive iodine ablation (iodine-131) in select patients and thyroxine therapy in most patients. Surgery is also the main treatment for medullary thyroid carcinoma, and kinase inhibitors may be appropriate for select patients with recurrent or persistent disease that is not resectable. Anaplastic thyroid carcinoma is almost uniformly lethal, and iodine-131 imaging and radioactive iodine cannot be used. When systemic therapy is indicated, targeted therapy options are preferred. This article describes NCCN recommendations regarding management of medullary thyroid carcinoma and anaplastic thyroid carcinoma, and surgical management of differentiated thyroid carcinoma (papillary, follicular, Hürthle cell carcinoma).


Assuntos
Adenocarcinoma , Iodo , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Adenocarcinoma/tratamento farmacológico , Carcinoma Neuroendócrino , Humanos , Iodo/uso terapêutico , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/terapia
11.
Cancer Causes Control ; 33(7): 939-950, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35554777

RESUMO

PURPOSE: There is limited information on how the COVID-19 pandemic has changed health behaviors among cancer patients. We examined changes in exercise behaviors since the pandemic and identified characteristics associated with these changes among cancer patients. METHODS: Cancer patients (n = 1,210) completed a survey from August to September 2020 to assess COVID-19 pandemic-related changes in health behaviors and psychosocial factors. Patients were categorized into three groups: exercising less, exercising did not change, and exercising more. Patient characteristics were compared by exercise groups. RESULTS: One-third of the patients reported a decreased amount of regular exercise, while 10% reported exercising more during the pandemic. Patients who exercised less were more likely to be unemployed/retired and have poor health status and psychosocial stressors such as disruptions in daily life while less likely to be former smokers (all p < 0.05). In contrast, patients who exercised more were younger, had stage IV diagnosis, and also reported disruptions in daily life (all p < 0.05). Patients who were living in rural areas were also more likely not to experience changes in exercise habits (all p < 0.05), although rural-urban status was not identified as a strong predictor. CONCLUSION: A significant proportion of cancer patients experienced changes in exercise habits, especially exercising less, during the first 6 months of the COVID-19 pandemic. Age, employment status, tumor stage, health status, smoking status, and psychosocial factors were associated with changes in exercise behaviors. Our results highlight the importance of promoting physical activity guidelines for cancer survivorship during the COVID-19 pandemic and may help improve the identification of cancer patients susceptible to exercising less.


Assuntos
COVID-19 , COVID-19/epidemiologia , Exercício Físico/psicologia , Comportamentos Relacionados com a Saúde , Humanos , Pandemias , Fumar/psicologia
12.
Infect Immun ; 90(5): e0062821, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35435726

RESUMO

Orientia tsutsugamushi is a genetically intractable obligate intracellular bacterium, causes scrub typhus, and has one of the largest known armamentariums of ankyrin repeat-containing effectors (Anks). Most have a C-terminal F-box presumed to interact with the SCF ubiquitin ligase complex primarily based on their ability to bind overexpressed Skp1. Whether all F-box-containing Anks bind endogenous SCF components and the F-box residues essential for such interactions has gone unexplored. Many O. tsutsugamushi Ank F-boxes occur as part of a PRANC (pox protein repeats of ankyrin-C-terminal) domain. Roles of the non-F-box portion of the PRANC and intervening sequence region (ISR) that links the ankyrin repeat and F-box/PRANC domains are unknown. The functional relevance of these effectors' non-ankyrin repeat domains was investigated. The F-box was necessary for Flag-tagged versions of most F-box-containing Anks to precipitate endogenous Skp1, Cul1, and/or Rbx1, while the ISR and PRANC were dispensable. Ank toxicity in yeast was predominantly F-box dependent. Interrogations of Ank1, Ank5, and Ank6 established that L1, P2, E4, I9, and D17 of the F-box consensus are key for binding native SCF components and for Ank1 and Ank6 to inhibit NF-κB. The ISR is also essential for Ank1 and Ank6 to impair NF-κB. Ectopically expressed Ank1 and Ank6 lacking the ISR or having a mutagenized F-box incapable of binding SCF components performed as dominant-negative inhibitors to block O. tsutsugamushi NF-κB modulation. This study advances knowledge of O. tsutsugamushi Ank functional domains and offers an approach for validating their roles in infection.


Assuntos
Orientia tsutsugamushi , Tifo por Ácaros , Repetição de Anquirina , Proteínas de Bactérias/metabolismo , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Orientia tsutsugamushi/genética
13.
J Rural Health ; 38(4): 886-899, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35243690

RESUMO

PURPOSE: The COVID-19 pandemic has disrupted many facets of life. We evaluated pandemic-related health care experiences, COVID-19 prevention behaviors and measures, health behaviors, and psychosocial outcomes among rural and urban cancer patients. METHODS: Among 1,472 adult cancer patients, who visited Huntsman Cancer Institute in the past 4 years and completed a COVID-19 survey (August-September 2020), we assessed the impact of the pandemic on medical appointments, prevention/health behaviors, and psychosocial factors, stratified by urbanicity. FINDINGS: Mean age was 61 years, with 52% female, 97% non-Hispanic White, and 27% were residing in rural areas. Rural versus urban patients were more likely to be older, not employed, uninsured, former/current smokers, consume alcohol, and have pandemic-related changes/cancellations in surgery appointments (all P<.05). Changes/cancellations in other health care access (eg, doctor's visits) were also common, particularly among urban patients. Urban versus rural patients were more likely to socially distance, use masks and hand sanitizer, and experience changes in exercise habits and in their daily lives (all P<.05). Less social interaction and financial stress were common among cancer patients but did not differ by urbanicity. CONCLUSIONS: These findings suggest that the COVID-19 pandemic had a substantial impact on cancer patients, with several challenges specific to rural patients. This comprehensive study provides unique insights into the first 6 months of COVID-19 pandemic-related experiences and continuity of care among rural and urban cancer patients predominantly from Utah. Further research is needed to better characterize the pandemic's short- and long-term effects on rural and urban cancer patients and appropriate interventions.


Assuntos
COVID-19 , Higienizadores de Mão , Neoplasias , Adulto , COVID-19/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/terapia , Pandemias , População Urbana
14.
Surg Clin North Am ; 102(2): 251-265, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35344696

RESUMO

Primary hyperparathyroidism can be asymptomatic or symptomatic, as well as classic, normocalcemic, or normohormonal. It is important to rule out other causes of hypercalcemia or hyperparathyroidism. Preoperative localization with imaging is necessary for a minimally invasive approach and can be helpful even if planning 4-gland exploration. There are a variety of intraoperative techniques that can assist with localization as well as confirming success. Standard of care remains surgical resection of affected glands. However, there are less invasive management strategies that can be considered for poor surgical candidates.


Assuntos
Hiperparatireoidismo Primário , Diagnóstico por Imagem , Humanos , Hiperparatireoidismo Primário/diagnóstico , Hiperparatireoidismo Primário/cirurgia
15.
Otolaryngol Head Neck Surg ; 167(3): 452-456, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35192398

RESUMO

OBJECTIVE: The objective of this study is to describe the operative success of completely buried free flaps and to determine the safety/reliability of using implantable dopplers for postoperative monitoring in completely buried free flaps. STUDY DESIGN: A retrospective chart review was conducted from 2014 to 2020. Patients were included who had implantable dopplers placed for monitoring a completely buried free flap without a visible skin paddle. SETTING: Single academic cancer hospital. METHODS: Patient charts were reviewed to determine flap viability after surgery, need for reoperation, and ability of implanted doppler probes to detected change in free flap status. RESULTS: A total of 65 patients were included. Locations of flaps were as follows: pharynx, 76.9%; skull base, 7.7%; trachea, 6.2%; esophagus, 4.6%; and facial reanimation, 4.6%. Types of free flaps performed included radial forearm (50.8%), anterolateral thigh (44.6%), and gracilis (4.6%). One patient (1.5%) returned to the operating room for vascular compromise, which was accurately detected by the implantable doppler and salvaged. All free flaps were viable upon hospital discharge based on clinical examination and implantable doppler signals. There were no complications related to implantable doppler use. CONCLUSIONS: Implantable dopplers are an effective method for evaluating postoperative success of completely buried free flaps. In our series utilizing implantable dopplers, buried free flap survival was higher than traditionally thought. The use of implanted dopplers for monitoring buried free flaps allows for an effective, cosmetically appealing, and simplified reconstructive technique.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Retalhos de Tecido Biológico/irrigação sanguínea , Humanos , Microcirurgia , Monitorização Fisiológica/métodos , Procedimentos de Cirurgia Plástica/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Ultrassonografia Doppler
16.
Clin Endocrinol (Oxf) ; 96(5): 734-742, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35067961

RESUMO

OBJECTIVE: The treatment of anaplastic thyroid cancer (ATC) has continued to rapidly evolve over time. Increased utilization of novel, personalized therapies based upon the tumour's somatic mutation status has recently been integrated. The aim of this case series is to describe a series of patients that underwent rapid genomic testing upon their diagnosis of ATC, allowing for the early integration of novel therapies. DESIGN: A fast track pathway for genomic tumour analysis of patients with ATC was implemented at a single academic cancer hospital in January of 2020. PATIENTS: All patients were evaluated by head and neck surgery, endocrinology, and medical oncology upon diagnosis of ATC. MEASUREMENTS: Genetic work-up was completed, which prompted a recommendation for dual BRAF/MEK inhibition with dabrafenib and trametinib for tumours with BRAF V600E mutation. For patients whose tumours were BRAF V600E wild-type, pembrolizumab with lenvatinib was offered. RESULTS: A total of four patients were included in this series. Two patients (50%) had tumours that were BRAF V600E positive. Among patients that were BRAF V600E positive, both patients initiated urgent dabrafenib and trametinib dual tyrosine kinase inhibitor (TKI) therapy; with one patient demonstrating near-complete clinical response allowing for posttreatment surgery, while the other demonstrated decreased tumour burden. Among patients who were BRAF V600E wild-type, lenvatinib and pembrolizumab were recommended off-label; one patient demonstrated decreased tumour burden, but developed severe pure red cell aplasia, while the other patient is demonstrating an early clinical response. CONCLUSIONS: The integration of early genomic analysis and personalized neoadjuvant TKI therapy into the treatment of ATC can greatly benefit patient care outcomes and optimize tumour control.


Assuntos
Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Humanos , Terapia de Alvo Molecular , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/genética , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
17.
Pathog Dis ; 79(7)2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34515306

RESUMO

Orientia tsutsugamushi is an obligate intracellular bacterium that causes scrub typhus, a potentially fatal rickettsiosis, and for which no genetic tools exist. Critical to addressing this technical gap is to identify promoters for driving expression of antibiotic resistance and fluorescence reporter genes in O. tsutsugamushi. Such promoters would need to be highly conserved among strains, expressed throughout infection, and exhibit strong activity. We examined the untranslated regions upstream of O. tsutsugamushi genes encoding outer membrane protein A (ompA), 22-kDa type-specific antigen (tsa22) and tsa56. The bacterium transcribed all three during infection of monocytic, endothelial and epithelial cells. Examination of the upstream noncoding regions revealed putative ribosome binding sites, one set of predicted -10 and -35 sequences for ompA and two sets of -10 and -35 sequences for tsa22 and tsa56. Comparison of these regions among geographically diverse O. tsutsugamushi patient isolates revealed nucleotide identities ranging from 84.8 to 100.0%. Upon examination of the candidates for the ability to drive green fluorescence protein expression in Escherichia coli, varying activities were observed with one of the tsa22 promoters being the strongest. Identification and validation of O. tsutsugamushi promoters is an initial key step toward genetically manipulating this important pathogen.


Assuntos
Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Orientia tsutsugamushi/genética , Regiões Promotoras Genéticas , Infecções por Rickettsia/microbiologia , Tifo por Ácaros/microbiologia , Animais , Antígenos de Bactérias/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Linhagem Celular , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Haplorrinos , Células HeLa , Humanos , Células THP-1
18.
Res Sq ; 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34580667

RESUMO

Purpose There is limited information on how the COVID-19 pandemic has changed health behaviors among cancer patients. We examined the impact of the pandemic on changes in exercise behaviors and identified characteristics associated with these changes among cancer patients. Methods Cancer patients (n = 1,361) completed a survey from August-September 2020 to assess COVID-19 pandemic-related changes in health behaviors and psychosocial factors. Patients were categorized into 3 groups: exercising less, exercising did not change, and exercising more. Patient characteristics were compared by exercise groups. Results One-third of the patients reported a decreased amount of regular exercise, while 11% reported exercising more during the pandemic. Patients who exercised less were more likely to be unemployed/retired, undergoing active treatment, and had increased pandemic-related alcohol consumption and psychosocial stressors such as loneliness and financial stress (all p < 0.05). In contrast, patients who exercised more were younger, female, full-time employed, did not consume alcohol, and had good health status and more social interactions (all p < 0.05). Patients who were living in rural areas and did not experience changes in daily life, were also more likely not to experience changes in exercise habits (all p < 0.05). Conclusion Our results indicate that a significant proportion of cancer patients experienced changes in exercise habits during the first 6 months of the COVID-19 pandemic. Age, sex, employment status, health status, alcohol consumption, and psychosocial factors were associated with changes in exercise behaviors. Providers should monitor for changes in health behaviors, such as exercise, because of their importance in improving cancer survivorship.

19.
J Histochem Cytochem ; 69(8): 523-534, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34339312

RESUMO

Radiation therapy-mediated salivary gland destruction is characterized by increased inflammatory cell infiltration and fibrosis, both of which ultimately lead to salivary gland hypofunction. However, current treatments (e.g., artificial saliva and sialagogues) only promote temporary relief of symptoms. As such, developing alternative measures against radiation damage is critical for restoring salivary gland structure and function. One promising option for managing radiation therapy-mediated damage in salivary glands is by activation of specialized proresolving lipid mediator receptors due to their demonstrated role in resolution of inflammation and fibrosis in many tissues. Nonetheless, little is known about the presence and function of these receptors in healthy and/or irradiated salivary glands. Therefore, the goal of this study was to detect whether these specialized proresolving lipid mediator receptors are expressed in healthy salivary glands and, if so, if they are maintained after radiation therapy-mediated damage. Our results indicate that specialized proresolving lipid mediator receptors are heterogeneously expressed in inflammatory as well as in acinar and ductal cells within human submandibular glands and that their expression persists after radiation therapy. These findings suggest that epithelial cells as well as resident immune cells represent potential targets for modulation of resolution of inflammation and fibrosis in irradiated salivary glands.


Assuntos
Tolerância a Radiação , Receptores de Quimiocinas/genética , Receptores de Formil Peptídeo/genética , Receptores Acoplados a Proteínas G/genética , Receptores do Leucotrieno B4/genética , Receptores de Lipoxinas/genética , Glândula Submandibular/efeitos da radiação , Células Acinares/citologia , Células Acinares/metabolismo , Células Acinares/efeitos da radiação , Adulto , Idoso , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Células Endoteliais/efeitos da radiação , Feminino , Raios gama , Expressão Gênica , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/metabolismo , Leucócitos Mononucleares/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Receptores de Quimiocinas/metabolismo , Receptores de Formil Peptídeo/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores do Leucotrieno B4/metabolismo , Receptores de Lipoxinas/metabolismo , Glândula Submandibular/citologia , Glândula Submandibular/metabolismo
20.
Facial Plast Surg Aesthet Med ; 23(6): 455-459, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33656928

RESUMO

Objectives: Self-inflicted facial gunshot wounds (GSWs) result in complex but consistent injuries that are often survivable. We suggest a novel method for rapid stratification into groups that may be associated with hospital course and cost after self-inflicted facial GSWs. Methods: This is retrospective review of self-inflicted facial GSWs between January 1, 2009, and December 31, 2018, at a tertiary academic center. Patients were given a penetrating trauma rapid estimated disablity (PRED) score (1-4) based solely on radiologic imaging injury patterns. Clinicopathologic factors were then compared between groups. Results: There were 2 PRED 1 patients (15.1%), 8 PRED 2 patients (29.6%), 5 PRED 3 patients (18.5%), and 12 PRED 4 patients (44.4%). An increased PRED score was statistically associated with increasing mean days in intensive care unit (2.5 PRED 1, 4.2 PRED 2, 6 PRED 3, 11.6 PRED 4, p = 0.001), mean length of hospitalization (5.5 PRED 1, 13.1 PRED 2, 25.6 PRED 3, 39.8 PRED 4, p = 0.007), and mean cost ($) of hospitalization (22,000 PRED 1, 29,000 PRED 2, 37,000 PRED 3, 63,000 PRED 4, p = 0.01). Conclusions and Relevance: The PRED score for self-inflicted GSWs to the face is strongly associated with length of hospital stay and cost of hospitalization.


Assuntos
Traumatismos Faciais/diagnóstico por imagem , Tentativa de Suicídio , Tomografia Computadorizada por Raios X , Índices de Gravidade do Trauma , Ferimentos por Arma de Fogo/diagnóstico por imagem , Adulto , Traumatismos Faciais/economia , Traumatismos Faciais/etiologia , Traumatismos Faciais/terapia , Feminino , Seguimentos , Custos Hospitalares/estatística & dados numéricos , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tentativa de Suicídio/economia , Utah , Ferimentos por Arma de Fogo/economia , Ferimentos por Arma de Fogo/etiologia , Ferimentos por Arma de Fogo/terapia
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