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1.
Am J Otolaryngol ; 45(4): 104282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38604102

RESUMO

PURPOSE: This study aims to evaluate how various demographic factors impact the stage at diagnosis and, therefore, prognosis of laryngeal cancer. MATERIALS AND METHODS: Using the National Cancer Database, 96,409 patients were diagnosed with laryngeal squamous cell carcinoma between 2004 and 2020. Early (stage 0 or I) vs. late-stage (stage IV) cancers were compared based on demographic variables utilizing Chi-square and multivariate analysis with a significance of p < 0.05. RESULTS: Female, Black, and generally older patients were more likely to have late-stage cancer than their counterparts. When compared with a community cancer program, patients treated at other facility types were more likely to be diagnosed late. Patients with private insurance, Medicare, or other government insurance were all less likely to have late-stage cancer compared to patients without insurance. Compared to patients in the lowest median household income quartile, patients in the third quartile and fourth quartile were diagnosed earlier. Patients living in an area with the lowest level of high school degree attainment were most likely to be diagnosed late. Living in a more populous area was associated with a lower chance of being diagnosed late. Increasing Charlson-Deyo Score was associated with a stronger likelihood of being diagnosed at a later stage. CONCLUSION: Patients who are female, Black, uninsured, have a low household income, live in less populated and less educated areas, are treated at non-community cancer programs, and have more comorbid conditions have later stage diagnoses. This data contributes to understanding inequities in healthcare.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Laríngeas , Estadiamento de Neoplasias , Humanos , Feminino , Masculino , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/epidemiologia , Idoso , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/epidemiologia , Estados Unidos/epidemiologia , Fatores Sexuais , Fatores Etários , Prognóstico , Idoso de 80 Anos ou mais , Demografia , Adulto , Fatores Socioeconômicos , Diagnóstico Tardio/estatística & dados numéricos , Bases de Dados Factuais
2.
Cureus ; 15(8): e44351, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37779816

RESUMO

Introduction Lung cancer is a prevalent and potentially lethal cancer. The stage at initial presentation for diagnosis predicts mortality and helps to guide treatment options. Thus, it is critical to determine what factors impact the stage of cancer at diagnosis. This study sought to determine if certain socioeconomic and demographic factors are associated with receiving an early (Stage 0-I) or advanced (Stage IV) diagnosis of non-small cell lung cancer (NSCLC). Methods Using the National Cancer Database (NCDB), 1,149,539 patients were identified as having an NCDB Analytic Stage Group diagnosis of Stage 0-I (early) versus Stage IV (advanced) NSCLC between 2004 and 2018. Patients with early and delayed diagnoses were compared based on specific characteristics including sex, race, ethnicity, number of comorbid conditions, insurance status, median annual income, level of education, geographic location, and reporting facility. Using IBM SPSS Statistics for Windows, Version 28 (Released 2021; IBM Corp., Armonk, New York, United States), the data underwent analysis using binary multivariate logistic regression, chi-square analyses, and one-way ANOVA. Results Factors associated with an advanced diagnosis of NSCLC include being male, Black, Native American, or Hispanic. Compared to patients with at least one comorbid condition, those without comorbid conditions are more likely to present with advanced disease. Patients with private insurance, Medicaid, Medicare, or other government insurance are all less likely to present with advanced-stage cancer than patients without insurance. Compared to patients in the lowest median household income quartile, those in the second and fourth quartiles are diagnosed earlier. Patients living in areas where a higher proportion of residents lack a high school diploma are more likely to present with advanced NSCLC. Additionally, living in the Midwest and Western United States and presenting to Community Cancer programs are associated with advanced disease at initial presentation. Conclusions Factors that were associated with the advanced presentation of NSCLC included being male, Black, Native American, or Hispanic, having a lack of comorbid conditions or insurance, earning a lower median annual income, and living in a zip code where a higher proportion of residents lack a high school diploma. Additionally, residing in the Midwest and Western United States and seeking care at Community Cancer programs were associated with advanced disease at initial presentation. Understanding that certain socioeconomic and demographic factors impact the stage at initial diagnosis of NSCLC can allow for targeted intervention strategies aimed at the most at-risk individuals, areas, and facilities.

3.
World J Clin Oncol ; 14(7): 259-264, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37583947

RESUMO

BACKGROUND: The incidence of anal cancer has been increasing in the United States. Smoking is a well-established risk factor; however, the impact of smoking on disease re-currence and outcome has not been well studied. The aim of this study was to assess the association between anal cancer recurrence and cigarette smoking. AIM: To investigate the relationship between cigarette smoking status and anal cancer treatment outcome. METHODS: The cancer registry from a single, community hospital was screened for patients with anal cancer between 2010 and 2021. The following characteristics were gathered from the database: Age; sex; cigarette smoking history; American Joint Committee on Cancer Clinical Stage Group; response to therapy; recurrence; time to recurrence; mortality; time to death; and length of follow-up. Patients were divided into the following groups: Current smokers; former smokers; and never smokers. SPSSv25.0 software (IBM Corp., Armonk, NY, United States) was used for statistical analysis. RESULTS: A total of 95 patients from the database met the screening criteria. There were 37 never smokers, 22 former smokers, and 36 current smokers. There was no difference between groups in regards to race or sex. There was no difference in the American Joint Committee on Cancer Clinical Stage Group between groups. The former smokers were significantly older when compared to never smokers and current smokers (66.5 ± 13.17 vs 57.4 ± 7.82 vs 63.7 ± 13.80, P = 0.011). Former smokers and current smokers had a higher recurrence rate compared to never smokers (30.8% and 20.8% compared to zero, P = 0.009). There was not a significant difference in recurrence between former smokers and current smokers. There was no difference in the mortality, non-response rate, or time to death between the groups. CONCLUSION: Our data contributes evidence that cigarette smoking status is associated with increased recurrence for patients with anal cancer.

4.
Cureus ; 15(5): e38471, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37153835

RESUMO

Anastomotic leaks are one of the most feared and morbid complications after colorectal anastomosis. Management of leaks depends on the severity of the leak and focuses on controlling sepsis and saving the anastomosis. The lower the anastomosis, the more amenable it is to transanal approaches for salvage. However, when a complication exists higher up in the rectum, the surgeon is more limited in the ability to visualize and intervene. With the advent of transanal minimally invasive surgery (TAMIS) and the advancement of endoscopic procedures, there are now more options for surgeons to visualize and intervene in anastomotic colorectal leaks. Prior reports have described the use of TAMIS for the management of anastomotic leaks in the acute phase. However, this same approach can be useful in the management of chronic leaks. This report highlights the benefit of TAMIS to allow visualization and marsupialization of a chronic abscess cavity following an anastomotic leak.

5.
J Palliat Med ; 26(8): 1139-1146, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37093019

RESUMO

Background/Objectives: Palliative care (PC) has been associated with reduced patient symptom burden, improved physician satisfaction, and reduced cost of care. However, its use in primary bone tumors has not been well classified. Design/Setting and Subjects: Patients diagnosed with primary malignant bone tumors (osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma) between 2004 and 2018 were identified in the National Cancer Database. Cross tabulations with chi-square analysis were performed to evaluate frequencies of PC use by patient, facility, and tumor characteristics. Multivariate logistic binary regression was performed to evaluate relationships between patient, treatment facility, and tumor characteristics and the use of PC. Results: Around 24,401 patients were identified. Overall, 2.52% had any form of PC utilization. Of those receiving PC, 55.5-65.1% were treated with only noncurative surgery, radiation, chemotherapy, or any combination of these modalities. Odds of PC utilization were decreased for patients with chordomas, patients living >24 miles from the treatment facility, or patients with private insurance, Medicare, or unknown insurance status. Odds of PC utilization were increased in patients with greater tumor diameter or unknown tumor size, tumors in midline, increased tumor grade, stage IV tumors, or living in urban areas. Conclusion: PC use in patients with primary bone tumors increases with tumor stage, tumor grade, tumor size, and if the tumor is midline, and in patients living in urban areas. However, overall utilization remains markedly low. Future studies should be done to investigate these patterns of care and help expand the utilization of PC.


Assuntos
Neoplasias Ósseas , Cordoma , Osteossarcoma , Sarcoma de Ewing , Humanos , Idoso , Estados Unidos , Cuidados Paliativos , Medicare , Sarcoma de Ewing/diagnóstico , Sarcoma de Ewing/patologia , Sarcoma de Ewing/cirurgia , Neoplasias Ósseas/diagnóstico , Osteossarcoma/terapia , Cordoma/cirurgia , Estudos Retrospectivos
6.
Cureus ; 15(2): e34819, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36919067

RESUMO

BACKGROUND: There are significant differences in prognosis for osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordomas based on the stage at diagnosis. The five-year survival of these bone cancers varies from 75-87% at an early stage of diagnosis and falls to 27-55% at a late stage of diagnosis. PATIENTS AND METHODS: This study retrospectively evaluated the odds of stage I vs stage IV cancer at the time of diagnosis in patients with primary malignant bone tumors (osteosarcoma, chondrosarcoma, Ewing sarcoma and chordoma) diagnosed in the National Cancer Database (NCDB) between 2004 and 2018. Cross tabulations with Chi-square analysis were performed to evaluate frequencies of different socioeconomic and geographical characteristics between patients with stage I vs stage IV cancer. Multivariable binary logistic regression was performed to evaluate relationships between socioeconomic and geographical factors and the odds of stage IV cancer at the time of diagnosis. Statistical significance was set at α = 0.05. RESULTS: 8882 patients with stage I and 3063 with stage IV primary malignant bone tumors were identified. The odds of stage IV bone cancer at diagnosis are increased for patients on Medicaid (odds ratio [OR] = 1.298, 95% confidence interval [CI]: 1.043-1.616) or Medicare (OR = 1.795, 1.411-2.284). Odds of stage IV bone cancer at diagnosis were decreased with female sex (OR = 0.733, 0.671-0.800), private insurance (OR = 0.738, 0.601-0.905), and those treated at community cancer programs (OR = 0.542, 0.369-0.797), comprehensive cancer program (OR = 0.312, 0.215-0.452), or academic/research facilities (OR = 0.370, 0.249-0.550). No significant relationship was identified between the stage at diagnosis and race, ethnicity, Charlson-Deyo score, or education level. Stage IV cancer at diagnosis showed was proportionally lower in chondrosarcomas (17.1%) and chordomas (2.1%) than osteosarcomas (45.0%) and Ewing sarcomas (35.8%). CONCLUSION: Odds of stage IV bone cancer at diagnosis are greater with male sex, Medicaid or Medicare insurance status, or treatment at community cancer programs. Providers should have a low suspicion for additional evaluation when treating patients with symptoms of bone cancer and should be aware of these disparities when treating people in these groups. This is to the authors' knowledge the first such study conducted through the NCDB.

7.
Am J Hosp Palliat Care ; 40(8): 926-935, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36067349

RESUMO

Background: Osteosarcoma is the most common form of bone cancer, but the utilization of palliative care (PC) in patients with this cancer has not previously been investigated in the National Cancer Database (NCDB). Methods: Patients diagnosed with osteosarcoma (2004-2017) were identified within the NCDB. Cross tabulations with Chi-square analysis were performed to evaluate frequencies of palliative care use by patient, facility, and tumor characteristics. Multivariate logistic binary regression was performed to evaluate relationships between patient, treatment facility, and tumor characteristics and the use of palliative care. Results: A total of 7498 patients were analyzed with 2.8% of patients diagnosed having any form of palliative care utilization. Of this group, 53.37% received PC within the first 12 months after diagnosis. Of the 2.8% of patients receiving PC the most common forms of PC utilized were non-curative symptom-directed surgery, radiation, or chemotherapy, or a combination of these modalities (56.7%). Palliative care usage was increased in patients with greater tumor diameter, tumors in the bones of the midline, or stage IV tumors. Palliative care usage was decreased in patients living within 25-49 miles of their treatment facility, those living in pacific states, those with chondroblastic osteosarcoma, or those with private insurance. Conclusion: Palliative care use in patients with osteosarcoma increases with tumor stage, tumor size, or more proximal tumors, but overall utilization remains markedly low. Future studies should further define these patterns of care and help expand the utilization of PC.


Assuntos
Neoplasias Ósseas , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Osteossarcoma , Humanos , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/terapia , Bases de Dados Factuais , Osteossarcoma/terapia , Cuidados Paliativos , Estudos Retrospectivos
8.
Cureus ; 14(5): e25525, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35800803

RESUMO

PURPOSE: Ewing sarcoma is a primary malignant bone tumor that manifests predominantly in the proximal long bones and pelvis and traditionally presents with nonspecific symptoms. This tumor preferentially affects children and young adults, occurring most often in patients of European descent. The most important established prognostic factor is the presence of metastasis at the time of diagnosis followed by primary site, size of the primary neoplasm, patient age, and lactate dehydrogenase (LDH) levels. To the authors' knowledge, this is the first study focused on the effects of socioeconomic and geographic factors on overall survival in Ewings sarcoma. METHODS: A total of 3,920 patients diagnosed with Ewing sarcoma were identified in the National Cancer Database (NCDB) using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) code 9260. Of these, 3,238 met the inclusion criteria and were analyzed. Descriptive statistics, Kaplan-Meier survival curves, and Cox regression tables were all performed using IBM SPSS Statistics for Windows, Version 27.0 (Released 2020; IBM Corp., Armonk, New York, United States). RESULTS: Univariate analysis showed greater mortality for patients of increasing age at the time of diagnosis, at two, five, and 10 years of follow-up, Black race patients at two years, Medicare insurance status at two years, urban or rural residence at two and 10 years, more advanced tumor stage at two and five years, and patients with a comorbidity score of ≥2 at two years. Multivariate analysis showed greater mortality at two years with increasing age, Black race, uninsured status, urban or rural residence, and increasing tumor stage. Mortality also increased for patients at five years of follow-up in patients with increasing age or more advanced tumor stage.  Conclusion: Patient mortality in the first two years after diagnosis is increased for patients of the Black race, those living in urban or rural areas, and for patients that are uninsured or using Medicare as their primary payor at the time of diagnosis. To improve patient outcomes, clinicians should recognize and address not only the unique biology of patients but also their unique challenges in access to healthcare. Patients and providers should work to elicit changes on an individual and community level to improve their personal health and the health of those around them.

9.
Cureus ; 14(4): e23984, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35573564

RESUMO

PURPOSE: To evaluate the educational content, quality, and reliability of YouTube videos regarding the Achilles tendon and Achilles tendon injuries. METHODS: The first 50 videos found on YouTube after searching "Achilles tendon" were evaluated and classified by content type and uploader source. Reliability and accuracy were assessed using the Journal of the American Medical Association (JAMA) benchmark criteria, nonspecific educational content was assessed via the Global Quality Score (GQS), and specific educational content was assessed using the Achilles Tendon Specific Score (ATSS). ANOVA was performed to determine differences in video reliability and educational content quality by video content type and source. Multivariate stepwise regressions were used to evaluate the effects of specific video characteristics on JAMA benchmark criteria, GQS, and ATSS. RESULTS: The 50 videos evaluated had a cumulative view total of 53,323,307, a mean of 1,066,466, and a range of 1,009 to 42,663,665 views per video. Most videos focused on disease-specific information (38%) and exercise training (22%). Most videos were uploaded by non-physicians (34%) or medical sources (health websites) (32%). A higher view ratio was an independent predictor of lower JAMA scores (lower reliability and accuracy) (standardized beta = -0.281, P = 0.048) and increased video duration was an independent predictor of greater GQS (standardized beta = 0.380, P = 0.007) and ATSS scores (standardized beta = 0.364, P = 0.009) (increased quality of nonspecific and specific educational content). CONCLUSION: Videos on YouTube regarding the Achilles tendon were viewed numerous times, but their educational content and reliability were poor. Providers treating patients for Achilles tendon-related pathologies should initiate a dialogue with patients about their use of internet sources and should educate them on their optimal usage. They should warn them of the low quality of YouTube-derived information and provide them with reliable sources that may better give them control over their own care.

10.
Chembiochem ; 23(6): e202100633, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35061295

RESUMO

The ubiquitin ligase C-terminus of Hsc70 interacting protein (CHIP) is an important regulator of proteostasis. Despite playing an important role in maintaining proteostasis, little progress has been made in developing small molecules that regulate ubiquitin transfer by CHIP. Here we used differential scanning fluorimetry to identify compounds that bound CHIP. Compounds that bound CHIP were then analyzed by quantitative ubiquitination assays to identify those that altered CHIP function. One compound, MS.001, inhibited both the chaperone binding and ubiquitin ligase activity of CHIP at low micromolar concentrations. Interestingly, we found that MS.001 did not have activity against isolated U-box or tetratricopeptide (TPR) domains, but instead only inhibited full-length CHIP. Using in silico docking we identified a potential MS.001 binding site on the linker domain of CHIP and mutation of this site rendered CHIP resistant to MS.001. Together our data identify an inhibitor of the E3 ligase CHIP and provides insight into the development of compounds that regulate CHIP activity.


Assuntos
Proteína C , Ubiquitina-Proteína Ligases , Proteína C/genética , Proteína C/metabolismo , Estrutura Terciária de Proteína , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
11.
Ann Thorac Surg ; 109(4): e251-e253, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31473180

RESUMO

Hiatal hernia is a common diagnosis. Unless symptomatic, most hiatal hernias are not repaired; in rare cases, however, severe complications can develop during conservative treatment. Although fecopneumothorax occurrence has been described in trauma and related to colonic pathology, it has not been described as occurring from spontaneous strangulation of a hiatal hernia. Regardless of the etiology, prompt recognition of the rare occurrence of fecopneumothorax is imperative. This report describes the presentation, diagnosis, and treatment of a patient presenting with a type IV hiatal hernia that resulted in colonic ischemia, perforation, and fecopneumothorax.


Assuntos
Fezes , Hérnia Hiatal/complicações , Pneumotórax/etiologia , Perfuração Espontânea/complicações , Hérnia Hiatal/diagnóstico , Hérnia Hiatal/terapia , Humanos , Masculino , Pneumotórax/diagnóstico , Pneumotórax/terapia , Perfuração Espontânea/diagnóstico , Perfuração Espontânea/terapia , Adulto Jovem
12.
J Gastrointest Surg ; 24(1): 88-97, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31432326

RESUMO

BACKGROUND: Surgery is common in patients with Crohn's disease and can contribute significantly to patient morbidity. The National Surgical Quality Improvement Program surgical risk calculator (NSQIP-SRC) that is currently utilized to predict surgical risk does not take Crohn's disease into account and, as a result, seems to underestimate risk in this patient population. This study aimed to evaluate the accuracy of the NSQIP-SRC in Crohn's disease patients and to evaluate the utility of disease severity scores in predicting surgical risk. METHODS: Between 2011 and 2017, there were 176 surgical cases involving Crohn's disease patients. Demographic data and 30-day surgical outcomes were collected. Disease severity scores including Harvey Bradshaw Index (HBI), Crohn's Disease Activity Index (CDAI), Simple Endoscopic Score for Crohn's Disease (SES-CD), and NSQIP-SRC risk percentages were calculated. RESULTS: Patients in remission based on HBI had a complication rate of 8.57% (n = 3), while those with mild or moderate-severe disease had rates of 33.33% (n = 11) and 38.46% (n = 20) respectively (p = 0.0045). In multivariable analysis, those with mild (OR; 8.37, 95% CI; 1.64, 42.78; p = 0.011) or moderate-severe (OR; 11.69, 95% CI; 2.42, 56.46; p = 0.002) disease had increased odds of complication compared to remission. Complication rate was not associated with NSQIP-SRC percent risk of any complication. CONCLUSION: NSQIP-SRC does not accurately predict risk in patients with CD undergoing surgery. Higher disease activity based on HBI is associated with increased odds of complication and may prove to be more predictive of surgical complication in the Crohn's patient population.


Assuntos
Doença de Crohn/cirurgia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Crohn/complicações , Doença de Crohn/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença
13.
Otol Neurotol ; 39(10): e964-e971, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30252797

RESUMO

OBJECTIVE: To determine if postlingually deaf adult cochlear implant (CI) users have better environmental sound awareness (ESA) compared with adult patients eligible for CIs who have not yet undergone implantation. STUDY DESIGN: Cross-sectional cohort study. SETTING: Tertiary referral center. PATIENTS: A group of 39 postlingually deaf adult patients who are experienced CI users (ECI), and a group of 20 postlingually deaf adult patients who are cochlear implant candidates (CIC) awaiting implantation. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURE: Environmental sound awareness as measured by accuracy (percent correct) using the computerized, Familiar Environmental Sounds Test-Identification (FEST-I). RESULTS: There was no significant difference between ESA in our sample of ECI users versus CIC patients. The ECI users scored an average FEST-I accuracy of 59.9% (SD 14.3). In comparison, the CICs had an average FEST-I accuracy of 54.7% (SD 26.4). This difference was not statistically significant. CONCLUSIONS: Our findings suggest that, despite the commonly held notion that improved ESA may be a benefit of cochlear implantation, our sample of ECI users did not demonstrate superior performance compared with CICs.


Assuntos
Percepção Auditiva/fisiologia , Implante Coclear , Implantes Cocleares , Surdez/fisiopatologia , Som , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Estudos Transversais , Surdez/reabilitação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pessoas com Deficiência Auditiva , Percepção da Fala/fisiologia
14.
Psychiatry Res ; 269: 345-353, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30173040

RESUMO

The neurocircuitries subserving affective and olfactory processes overlap, are sexually dimorphic, and show disruptions in schizophrenia, suggesting their intersection may be a window on the core process producing psychosis. This study investigated diagnostic and sex differences in hedonic judgments of odors and smell identification in 26 schizophrenia cases and 27 healthy controls. Associations between olfaction measures and psychiatric symptoms were also examined. Cases and controls had similar identification accuracy of unpleasant odors, but cases were significantly less accurate in naming pleasant odors. In cases, greater negative symptom severity was related to abnormal hedonic judgments; specifically, higher pleasantness ratings for unpleasant odors and higher unpleasantness ratings for pleasant odors. Greater positive symptom severity was associated with lower pleasantness ratings for neutral odors. Regarding sex differences, male cases and female controls rated pleasant odors as significantly more unpleasant than male controls. Correlations between depression severity and pleasantness ratings of neutral odors were in opposite directions in male and female cases. These results suggest that a normal sexual dimorphism in the circuitry for hedonic odor judgments may interact with schizophrenia pathology, supporting the utility of olfactory hedonics as a sex-specific biomarker of this pathology.


Assuntos
Anedonia , Percepção Olfatória , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Fatores Sexuais , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Julgamento , Masculino , Negativismo , Odorantes/análise , Índice de Gravidade de Doença , Olfato
15.
Surg Oncol Clin N Am ; 27(3): 463-475, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29935683

RESUMO

The peritoneum protects the intraabdominal organs. This function is exploited by aggressive cancers originating from organs within the abdomen, resulting in peritoneal metastasis. We discuss genomic variants that may lead to peritoneal metastasis from multiple cancers. Peritoneal malignancies are attributed to epithelial-mesenchymal transition. These metastatic lesions harbor similar genetic mutations to the primary tumor yet may manifest clone-specific aberrations that promote propagation. Peritoneal metastasis are increasingly being treated with surgical resection as an adjunct to radiation, chemotherapy, and other biologic therapies. We describe genetic and genomic variances that are predictive markers for metastasis and burgeoning indicators for peritoneal malignancies.


Assuntos
Biomarcadores Tumorais/genética , Genômica/métodos , Neoplasias Peritoneais/genética , Humanos , Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/terapia
16.
Front Psychol Behav Sci ; 3(1): 1-17, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-25419548

RESUMO

While researchers have for decades considered the role of social factors, endocrinology, neural function, hippocampal integrity, and cognition in the development of schizophrenia, there has been a relative paucity of studies considering the participation of the stress cascade in the interplay of these elements. As described in this review, stressful exposures and stress sensitivity may plausibly be argued to play a role in the etiology, neurobiology, and course of schizophrenia and related psychotic disorders. Notably, research conducted over the last decade has made it increasingly clear that childhood traumatic experiences represent a prominent risk factor for the development of psychotic disorders, including schizophrenia. Accumulating evidence suggests that this relationship is mediated by the development of a neuropathological stress response, involving HPA axis dysregulation, aberrant functioning of different neurotransmitter systems, hippocampal damage, and memory deficits. However, it remains difficult to identify exact causal pathways linking early trauma to schizophrenia, including to the individual symptoms associated with the disorder. In addition to the strong association among early trauma, stress sensitization, and positive symptoms in schizophrenia, there is also evidence indicating that the negative and cognitive symptoms are related to these factors. However, the emergence of these symptoms may lie on a distinct and non-interacting pathway in relation to the development of the positive symptoms. The natural increases in stress sensitivity and HPA axis activity during adolescence may act on already maladaptive stress circuitry resulting from early trauma and/or a genetic predisposition to produce full blown stress sensitization and cause epigenetic effects, such as the altered methylation of different genes, that lead to schizophrenia or other psychiatric illnesses.

17.
Nat Genet ; 46(11): 1170-2, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25305755

RESUMO

Neurofibromatosis 1 is a hereditary syndrome characterized by the development of numerous benign neurofibromas, a small subset of which progress to malignant peripheral nerve sheath tumors (MPNSTs). To better understand the genetic basis for MPNSTs, we performed genome-wide or targeted sequencing on 50 cases. Sixteen MPNSTs but none of the neurofibromas tested were found to have somatic mutations in SUZ12, implicating it as having a central role in malignant transformation.


Assuntos
Neurilemoma/genética , Complexo Repressor Polycomb 2/genética , Sequência de Bases , Biologia Computacional , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Mutação/genética , Proteínas de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Sequência de DNA , Fatores de Transcrição
18.
Pathog Dis ; 72(2): 104-10, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25044984

RESUMO

The gut immune system is complex, and dysregulation leads to a number of disorders including inflammatory bowel syndrome and (in livestock) Johne's disease. Previous work has demonstrated that males and females respond differently to treatment with pathologic and probiotic microorganisms, suggesting that a 'one-size-fits-all' approach to treat GIT inflammation may be inadequate. While we had observed significant differences between males and females in terms of cytokine production, it remains unclear how these changes occur. To better understand the mechanisms, transcript expression of genes important to gut immunoregulation were monitored from male and female BALB/c mice consuming the probiotic Lactobacillus animalis (1 × 10(6) CFU g(-1) ) and infected with the gut pathogen, Mycobacterium avium subspecies paratuberculosis (1 × 10(7) CFU). Expression of transcripts analyzed included those important to the immune system, intestinal cell differentiation, and/or regulation. Males generally displayed increased expression of Th 2 and B-cell mediators, and females showed repressed cytokine expression after MAP infection (IL-6, TNF-α, IL-1 among others). Additionally, regulation of pro-inflammatory mediators in female mice consuming probiotics suggests females responded positively to L. animalis when compared to males. Therefore, we speculate that studying mechanistic changes associated with sex and immunoregulation in gastrointestinal tissues could further elucidate host response to microorganisms.


Assuntos
Citocinas/biossíntese , Trato Gastrointestinal/imunologia , Lactobacillus/imunologia , Mycobacterium avium subsp. paratuberculosis/imunologia , Probióticos/administração & dosagem , Animais , Feminino , Perfilação da Expressão Gênica , Masculino , Camundongos Endogâmicos BALB C , Fatores Sexuais
19.
PLoS One ; 9(6): e100930, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24979717

RESUMO

Dietary exposure to aflatoxin B1 (AFB1) is detrimental to avian health and leads to major economic losses for the poultry industry. AFB1 is especially hepatotoxic in domestic turkeys (Meleagris gallopavo), since these birds are unable to detoxify AFB1 by glutathione-conjugation. The impacts of AFB1 on the turkey hepatic transcriptome and the potential protection from pretreatment with a Lactobacillus-based probiotic mixture were investigated through RNA-sequencing. Animals were divided into four treatment groups and RNA was subsequently recovered from liver samples. Four pooled RNA-seq libraries were sequenced to produce over 322 M reads totaling 13.8 Gb of sequence. Approximately 170,000 predicted transcripts were de novo assembled, of which 803 had significant differential expression in at least one pair-wise comparison between treatment groups. Functional analysis linked many of the transcripts significantly affected by AFB1 exposure to cancer, apoptosis, the cell cycle or lipid regulation. Most notable were transcripts from the genes encoding E3 ubiquitin-protein ligase Mdm2, osteopontin, S-adenosylmethionine synthase isoform type-2, and lipoprotein lipase. Expression was modulated by the probiotics, but treatment did not completely mitigate the effects of AFB1. Genes identified through transcriptome analysis provide candidates for further study of AFB1 toxicity and targets for efforts to improve the health of domestic turkeys exposed to AFB1.


Assuntos
Aflatoxina B1/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Doenças das Aves Domésticas/genética , Probióticos/farmacologia , Transcriptoma , Aflatoxina B1/isolamento & purificação , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Aspergillus/química , Aspergillus/patogenicidade , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Perfilação da Expressão Gênica , Glicoproteínas/genética , Glicoproteínas/metabolismo , Lactobacillus/fisiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Metionina Adenosiltransferase/genética , Metionina Adenosiltransferase/metabolismo , Doenças das Aves Domésticas/induzido quimicamente , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/patologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Perus
20.
Schizophr Res ; 157(1-3): 63-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24910446

RESUMO

Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a Rapid Serial Visual Presentation of pictures. Target stimuli were either positive or negative, or neutral images presented at either 200ms or 700ms lag. Additionally, a visual hedonic task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200ms and 700ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700ms lag condition and fewer negative images under the 200ms lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder.


Assuntos
Atenção , Emoções , Memória , Transtornos Psicóticos/psicologia , Esquizofrenia , Psicologia do Esquizofrênico , Adulto , Nível de Alerta , Intermitência na Atenção Visual , Computadores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Testes Neuropsicológicos , Estimulação Luminosa , Detecção de Sinal Psicológico , Percepção Visual
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