RESUMO
The behaviour of the tompot blenny Parablennius gattorugine was studied by underwater observation and photography on the south-west coast of the UK over an 11 year period, with >50 individuals identified at two locations by their distinctive skin markings. Observations showed males engaging in rapid swimming behaviour when approached by a female, and younger males using alternative 'sneaker' tactics before becoming 'bourgeois' territory-holders. The noninvasive recognition technique also facilitated detailed observations on territory retention (up to 7 years) and agonistic behaviours among both males and females.
Assuntos
Perciformes , Reprodução , Masculino , Feminino , Animais , Comportamento Social , Comportamento Sexual Animal , Comportamento de Nidação , BiologiaRESUMO
WHAT IS KNOWN AND STUDY OBJECTIVE: Carfilzomib is a newer drug approved for the treatment of relapsing and refractory multiple myeloma. It has been rarely associated with acute liver failure (ALF). CASE SUMMARY: We present a case of 58-year-old man presenting with abnormal liver function tests and subsequently diagnosed with ALF due to carfilzomib. Liver enzymes improved significantly after discontinuation of the drug. WHAT IS NEW AND CONCLUSION: Even though ALF due to carfilzomib has been documented rarely in clinical studies, no detailed case report has been published so far. Patients on carfilzomib should be monitored for ALF, and prompt discontinuation of drug is necessary in such cases.
Assuntos
Antineoplásicos/efeitos adversos , Falência Hepática Aguda/induzido quimicamente , Mieloma Múltiplo/tratamento farmacológico , Oligopeptídeos/efeitos adversos , Antineoplásicos/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Humanos , Falência Hepática Aguda/patologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/administração & dosagemRESUMO
African Americans (AA) have a high incidence of risk factors associated with MASLD (metabolic dysfunction-associated steatotic liver disease); the AA population has a lower incidence of MASLD and MASH (metabolic-associated steatotic hepatitis) than Caucasian and Hispanic Americans (non-AA). We investigated if underlying risk factor variation between AA and non-AA individuals could provide a rationale for the racial diversity seen in MASLD/MASH. Using ICD-10 codes, patients from 2017 to 2020 with MASLD/MASH were identified and confirmed to have either MASLD or MASH. Despite the large (>80%) AA population in our clinics, only 54% of the MASLD/MASH patients were African American. When the non-invasive NAFLD Fibrosis Scores (NFS) evaluated at early diagnosis were compared to the most recent values, the only increase in fibrosis score by NFS over time was in non-AA MASH patients. The increase in fibrosis only in non-AA MASLD patients is consistent with racial disparity in the disease progression in non-AA as compared to AA patients. Even with the large proportion of AA patients in our study, there was no significant racial disparity in the earliest assessment of either risk factors, laboratory values, or fibrosis scores that would account for racial disparity in the development and progression of MASLD.
RESUMO
PURPOSE: This study tested the hypothesis that our predominately AA medical center population would demonstrate a decline in HCV-driven HCC diagnosis following the initiation of DAA treatment in 2014. Also evaluated was whether achieving an SVR prior to diagnosis of HCC improved outcomes in patients who had an HCV diagnosis after completion of treatment. METHODS: All patients with HCC seen at the Detroit Medical Center from 2009 to 2021 were identified using ICD-10 codes, and medical records were evaluated. Outcomes were evaluated as either alive or death/hospice as of December of 2022. RESULTS: There were 461 patients with HCC of whom 433 (94%) had racial information in the database (AA = 351; non-AA = 82). HCC incidence regardless of race peaked in 2017, with a subsequent decline through 2021. HCV as a risk factor was higher in AA as compared to non-AA (85% vs. 53% p = 0.0001). Outcome (alive vs. death/hospice) was better for SVR patients compared to untreated patients (54% vs. 19%; p = 0.0009). HCC patients who achieved SVR also had better liver function at diagnosis as defined by Child-Pugh score (74% vs. 49% Class A p = 0.04) at the time of diagnosis. CONCLUSIONS: Racial disparity in HCC etiology was confirmed with AA more likely to have HCV than non-AA. The reduction in HCC patients with HCV confirms the impact of DAA treatment and prior successful treatment of HCV yields better outcomes. Increasing HCV treatment rates especially in AA patients will have a major impact on HCC development and treatment outcomes. WHAT IS KNOWN: ⢠African Americans are more likely to have HCV infection as compared to non-AA. ⢠Hepatocellular carcinoma is increasing in incidence in the US. ⢠The role of HCV in the development of HCC remains to be further investigated. WHAT IS NEW: ⢠HCC diagnosis in a single urban medical center study increased from 2009 as a result of HCV as a risk factor. ⢠HCC declined post 2018 due primarily to a reduction in HCV infection as the risk factor. ⢠African Americans were more likely to have HCV as the risk factor as compared to non-AA patients who were more likely to have no known risk factor on record (i.e., cryptogenic).
Assuntos
Antivirais , Negro ou Afro-Americano , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Masculino , Feminino , Negro ou Afro-Americano/estatística & dados numéricos , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Idoso , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Estudos Retrospectivos , Incidência , Fatores de Risco , Hepacivirus/isolamento & purificação , Hepacivirus/efeitos dos fármacos , Resposta Viral Sustentada , Hepatite C/tratamento farmacológico , Hepatite C/complicações , Hepatite C/epidemiologia , Hepatite C/virologiaRESUMO
Introduction Direct-acting antiviral (DAA) treatment increased the sustained viral response (SVR) rate of patients with the hepatitis C virus (HCV) and eliminated response disparities between African American (AA) and non-AA patients seen with interferon (IFN). The aim of this study was to compare 2019 HCV patients (DAA era) to patients from January 1, 2002 and December 31, 2003 (IFN era) in our predominantly AA clinic population. Methods We extracted data on 585 HCV patients seen in 2019 (DAA era) and compared them to 402 patients seen in the IFN era. Results Most HCV patients were born between 1945 and 1965, but in the DAA era more younger patients were identified. Non-AA patients in both eras were less likely to be infected with genotype 1 compared to AA (95% vs 54%, P<0.001). Fibrosis was not increased in the DAA Era as compared to the IFN era as assessed either by serum-based assays (APRI, FIB-4) or transient elastography (FibroScan) (DAA era) vs biopsy (IFN era). More patients were treated in 2019 compared to 2002-2003 (159/585=27% vs 5/402=1%). For untreated patients, subsequent treatment within one year of the initial visit was low and similar in both eras (35%). Conclusion There continues to be a need to screen patients born between 1945 and 1965 for HCV as well as to identify increasing numbers of patients below this age cohort. Even though current therapies are oral, highly effective, and can be 8-12 weeks in duration, significant numbers of patients were not treated within a year of first visit.
RESUMO
OBJECTIVE: IRX-2, a primary cell-derived biologic with pleotropic immune activity, was shown to induce increased lymphocyte infiltrations into the tumor of patients with head and neck squamous cell cancer (HNSCC) after 10 days of neoadjuvant therapy (Berinstein et al. 2011). In the same patients enrolled in the Phase II study, peripheral blood lymphocyte subsets were monitored pre- and post-IRX-2 therapy to evaluate changes induced by IRX-2. METHODS: Absolute lymphocyte numbers were determined in whole blood using the TetraONE System. Lymphocytes were further separated on Ficoll-Hypaque gradients and evaluated by multiparameter flow cytometry. Lymphocyte numbers, including regulatory T cells (Treg) and naïve, memory and effector T cells, were compared in pre- and post-therapy specimens. RESULTS: Total lymphocyte numbers remained unchanged after IRX-2 therapy. Significant changes occurred in numbers of circulating B cells and NKT cells, which decreased following IRX-2 therapy. The frequency of circulating Treg (CD4(+)CD25(high)) remained unaltered (e.g., 6.7 ± 0.6% vs. 7.5 ± 0.8%; means ± SEM) as was the CD8(+)/Treg ratio (6.6 before and 6.7 after IRX-2 therapy). The mean absolute number of CD3(+)CD45RA(+)CCR7(+) (naïve) T cells was decreased after IRX-2 therapy but numbers of total memory (i.e., central and peripheral) and terminally differentiated T cells were unchanged. CONCLUSIONS: IRX-2-mediated reductions in B and NKT cell numbers in the blood suggest a redistribution of these cells to tissues. A decrease in naïve T cells implies their up-regulated differentiation to memory T cells. Unchanged Treg numbers after IRX-2 therapy indicate that IRX-2 does not expand this compartment, potentially benefiting anti-tumor immune responses.
Assuntos
Carcinoma de Células Escamosas/terapia , Citocinas/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Terapia Neoadjuvante , Subpopulações de Linfócitos T/efeitos dos fármacos , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/imunologia , Citocinas/administração & dosagem , Citocinas/imunologia , Citocinas/farmacologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/imunologia , Humanos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologiaRESUMO
Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists. Relative to pretreatment biopsies, increases in lymphocyte infiltration (LI) were seen using H and E or immunohistochemistry. CD3+ CD4+ T cells and CD20+ B cells were primarily found in the peritumoral stroma and CD3+ CD8+ T cells and CD68+ macrophages were mainly intratumoral. LI in the surgical specimens were associated with reductions in the primary tumor size. Improved survival at 5 years was correlated with high overall LI in the tumor specimens. Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor.
Assuntos
Citocinas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/terapia , Imunoterapia , Linfócitos do Interstício Tumoral/imunologia , Adulto , Idoso , Citocinas/administração & dosagem , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Análise de SobrevidaRESUMO
Background Coronary artery disease (CAD) is associated with celiac disease (CD) with limited evidence. However, the common risk factors linking CD and CAD are still lacking in the literature. Known CAD risk factors include hypertension, hyperlipidemia, type 2 diabetes, obesity, and tobacco use. Common risk factors linking CD and CAD are poorly documented. Objective There are three objectives: Firstly, to evaluate potential demographic differences between CD patients with CAD and without CAD. Secondly, to analyze the risk factors of CAD in CD patients. Lastly, to compare CD-CAD and matched non-CD CAD to determine whether there are additional CAD risks in individuals with CD. Methods The study is a nationwide retrospective case-control study. The National Inpatient Sample (NIS) database was used to identify patients admitted between 2016 and 2018 with a principal or secondary diagnosis of CD. We analyzed sociodemographic and clinical risk factors of CAD in CD patients and compared the CD-CAD population with the matched non-CD CAD cohort. Results Out of 23,441 hospitalizations with CD in 2016-2018, 4244 (18%) were found to have CAD. Established CAD risk factors identified in CD patients included hypertension, hyperlipidemia, type 2 diabetes, and a family history of CAD. In contrast, tobacco use is not a CAD risk factor in CD patients. Female patients with CD had 55% lesser odds of CAD than male patients. The odds of CAD in CD patients with hyperlipidemia were five times higher, 1.2 times higher with essential hypertension, and two times higher with type 2 diabetes. Patients with CAD had a higher prevalence of iron deficiency anemia (9.33% CD-CAD and 8.28% non-CAD CD Vs. 7.32% non-CD CAD). Conclusions Our study confirms that, as with non-CD individuals, males and the White race are at increased CAD risk in the CD population. CD-CAD patients have a higher hyperlipidemia prevalence than non-CD CAD patients. CD patients with type 1 diabetes have an early diagnosis of CAD compared to CD patients with type 2 diabetes. Iron deficiency anemia is a statistically significant risk factor for CAD in CD patients.
RESUMO
INTRODUCTION: Bowel preparation quality in colonoscopy is one of the most essential components of quality assessment. According to the latest guidelines, inadequate bowel preparation warrants repeat colonoscopy in less than a year. Our aim was to investigate the role of bowel preparation in adenoma detection rate (ADR), its relationship with patients' demographics, and compliance with subsequent surveillance recommendations with guidelines. METHODS: This is a retrospective chart review study. Bowel preparation quality was divided into three categories: high, intermediate, and low. ADR and polyp detection rates (PDR) were calculated as the number of patients with adenoma or polyp divided by the total number of patients. RESULTS: Among 1,062 patients (934 African American and 128 non-African American) 81%, 11%, and 8% had high, intermediate, and low-quality bowel preparations, respectively. Race, gender, age, type of endoscopist, and body mass index did not play any role in bowel preparation quality. ADR and PDR were significantly higher in African Americans as compared to non-African Americans. ADR was significantly lower in the low-quality as compared to the high- and intermediate-quality bowel preparations (OR=2.13; p=0.0032). Bowel preparation quality was not correlated with subsequent follow-up recommendations. Academic gastroenterologists and surgeons had the highest and lowest compliance with surveillance guidelines, respectively. CONCLUSIONS: Racial and gender disparity appears to have no meaningful effect on the quality of bowel preparation. Only two categories (adequate [high/intermediate] or inadequate [low-quality]) may be used for follow-up recommendations. Non-compliance with surveillance guidelines is concerning and may inadvertently increase the interval risk of colorectal cancer.
RESUMO
Introduction Quality metrics of colonoscopy should be routinely monitored with a focus on optimizing the patient's subsequent risk of colorectal cancer development. Documentation of bowel preparation, adenoma detection rate (ADR), and post-colonoscopy follow-up recommendations are three of the most important quality indicators for colonoscopy, but significant improvement has been challenging to achieve. The goal of this study is to determine whether the publication of colonoscopy quality indicator guidelines in 2015 resulted in an improvement in quality measures of physicians in our endoscopy suite as compared to before. Methods We reviewed the electronic medical records of patients who underwent a screening or surveillance colonoscopy in 2014 and 2017. Colonoscopies were performed in an open-access medical center endoscopy suite, staffed by three groups of physicians (academic gastroenterologists (AGs), non-academic gastroenterologists (non-AGs), and surgeons). We gathered demographic data, bowel preparation reports, follow-up recommendations, and notice to patient's primary care physician, and calculated ADR for patients. Age- and gender-matched patients in both years were analyzed for ADR. These data were further subcategorized for each group of physicians. Results There were 553 patients in 2014 and 1,095 in 2017. Overall, male gender and African American race constituted the majority of patients in both years. Among age- and gender-matched patients in 2014 and 2017 (412 and 243 patients, respectively), ADR within each group of endoscopists was not significantly different between these two years (AGs 44% vs. 50%; non-AGs 32% vs. 27%; surgeons 25% vs. 21%; p>0.05 for all). However, in 2014 and 2017, ADR was significantly higher in the AG group as compared to the non-AG group and surgeons (p<0.006 and p<0.0004, respectively). Reporting of bowel preparation quality (82% vs. 87%) and documenting the recommended period for follow-up surveillance colonoscopy in the report (68% vs. 78%) improved between 2014 and 2017 (p=0.002 and p=0.0001, respectively). Correct recommendations for follow-up surveillance colonoscopy only improved significantly in the AG group (74% in 2014 as compared with 82% in 2017, p=0.003). Conclusion Based on the current guidelines, AG physicians are far exceeding the target ADR goals, and are superior compared to other groups of endoscopists. Although improvements were noted after guideline publications, areas of needed improvement with respect to meeting gastroenterology society guidelines for quality remained. The fact that individual physicians are performing and billing in an endoscopy suite staffed and equipped by a medical center creates an environment where responsibility for improvement in quality cannot be readily assigned.
RESUMO
PURPOSE: Surveillance, treatment, and outcomes for African-American (AA) populations with hepatocellular carcinoma (HCC) remain under evaluated. This study evaluated demographics, surveillance, therapy, and outcomes for a predominately AA population. METHODS: The electronic medical records of a large health-care provider were used to identify 274 patients with visits for HCC between 2010 and 2017. Tumor size at diagnosis was defined by imaging with ≤ 5 cm being defined as "small." Surveillance for HCC was defined based on ultrasound (US) assessments. RESULTS: Patients were primarily AA (78%) and male (76%) with an average age at diagnosis of 62 years. Hepatitis C virus (HCV) was more likely to be a risk factor for the development of HCC in AA as compared to non-AA (92% vs 67%; p < 0.005). Surveillance rates were low (16% for AA vs 7% for non-AA). An aspartate aminotransferase platelet ratio index (APRI) value > 0.7 within 2 years of tumor diagnosis was a strong predictor for the risk of the development of HCC (86% AA vs 79 % non-AA). In this study, race was not a factor in treatment or outcomes, and most patients received tumor ablative treatment. CONCLUSION: Given the low surveillance rates and the demonstrated increased survival for patients with small tumors, ways to increase surveillance must be initiated. The results of this study demonstrate the need for physician/patient education on the importance of surveillance US. Further, this study supports routine assessment of APRI in AA patients in an effort to identify patients in whom intensive surveillance will significantly improve earlier detection of tumors.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Carcinoma Hepatocelular/mortalidade , Etnicidade/estatística & dados numéricos , Disparidades em Assistência à Saúde , Neoplasias Hepáticas/mortalidade , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Terapia Combinada , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Child and adolescent mental health disorders are present in around 10% of the population. Research indicates that many young people possess negative attitudes towards mental health difficulties among peers. AIMS: To assess the impact of a mental health teaching programme on adolescent pupils' understanding. METHOD: Two-group pre-test-post-test control group study in two English secondary schools. Experimental classes (School E) received a six-lesson teaching intervention on mental health; control classes (School C) did not. Participants were 14- and 15-year-old pupils. The intervention consisted of six lessons on mental health issues common to young people: stress; depression; suicide/self-harm; eating disorders; being bullied; and intellectual disability. School C was given access to these lesson plans and materials on completion of the study. Understanding was measured at two time points, Time 1 (T(1)) and Time 2 (T(2)), 8 months apart, by a Mental Health Questionnaire. Behavioural, emotional and relationship strengths and difficulties were measured by the self-rated Strengths and Difficulties Questionnaire (SDQ) with five subscales: hyperactivity, emotional symptoms, conduct problems, peer problems and prosocial behaviour. RESULTS: At T(2), pupils in School E compared with those in School C showed significantly more sensitivity and empathy towards people with mental health difficulties. They also used significantly fewer pejorative expressions to describe mental health difficulties. There was a significant reduction in SDQ scores on conduct problems and a significant increase on prosocial behaviour among School E pupils compared with controls. Pupils valued the intervention highly, in particular the lessons on suicide/self-harm. CONCLUSIONS: Teaching 14- and 15-year-olds about mental health difficulties helps to reduce stigma by increasing knowledge and promoting positive attitudes. The intervention also reduced self-reported conduct problems and increased prosocial behaviour. Generally, participating pupils were positive about the importance of lessons on mental health, and said that they had learnt much about the lesson topics.
Assuntos
Educação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Transtornos Mentais/psicologia , Estudantes/psicologia , Adolescente , Inglaterra , Humanos , Transtornos Mentais/fisiopatologia , Avaliação de Programas e Projetos de Saúde , Instituições Acadêmicas , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVE: The role of EUS-FNA biopsy (EUS-FNAB) for detection of metastatic lesions (mets) to adrenals has not been evaluated systematically. Our aim is to systematically evaluate the performance characteristics of EUS-FNAB in detecting metastasis to the adrenal glands. MATERIALS AND METHODS: We performed a systematic search on PubMed and OvidSP from January 1990 to July 2016 using various search terms for EUS and adrenal lesion. Only articles published in English literature were included in the study. Studies with fewer than 10 patients were excluded from the study. Publication bias was assessed using Begg-Mazumdar test and visual inspection of funnel plots. RESULTS: Eight studies including 360 adrenal lesions that underwent EUS-FNAB were identified. Of these, 137 FNABs were conclusive for malignancy. Sensitivity of EUS-FNAB in detecting metastasis to the adrenals was 95% (95% confidence interval [CI]: 90%-98%) and specificity was 99% (95% CI: 96%-100%). Pooled positivity of EUS-FNAB in detecting lung cancer metastasis to the adrenals was 44% (95% CI: 31.5%-57.3%). No evidence of publication bias was noted. CONCLUSION: Our study demonstrates that EUS-FNAB is highly sensitive and specific in detecting metastasis to adrenals. It also shows that up to about half of the patients with lung cancer and adrenal lesions on imaging have metastasis, a finding with profound implications on lung cancer staging and treatment.
RESUMO
BACKGROUND: Screening colonoscopy aims to interrupt the adenoma-carcinoma sequence by removing all precancerous adenomatous polyps. Adenomatous polyp detection rate (ADR) can vary between endoscopists as well as between race, age, and risk of colorectal cancer (CRC). The purpose of this study was to compare ADR among academic gastroenterologists (A-GI), non-A-GI, and surgeons for endoscopies performed in the same endoscopic suite of a large medical center with a predominately African American (AA) population. METHODS: All screening colonoscopies performed in 2014 for patients aged 62-76 years were identified using the electronic medical records data. Patients with average risk and high risk of CRC defined as having a 'personal history of polyps' or 'family history of CRC', and history of ulcerative colitis and Fecal Occult Blood Test/Fecal Immunochemical Test (FOBT/FIT) positivity were included. Patients with incomplete colonoscopy (defined as failing to achieve cecal intubation or poor preparation) and unrecovered tissue biopsy were excluded. ADR was calculated for three groups of endoscopists: A-GIs, non-A-GIs, and surgeons. RESULTS: A total of 573 screening colonoscopies was analyzed. The endoscopists comprised five A-GIs, eight non-A-GIs, and six surgeons. The majority of patients were of AA decent (71%), female (54%) with an average age of 66 years. Patients classified as average risk comprised 79% of the population. Most of the colonoscopies were performed by A-GI (n=339), followed by non-A-GI (n=144), and surgeons (n=90). The ADR for A-GI was 50% as compared to 32% for non-A-GI (p<0.001) and 25% for surgeons (p<0.001). Also, A-GI were more likely to identify ≥3 adenomas during screening colonoscopies. Significant differences were observed (p<0.001) in the mean time of colonoscopy for A-GI (30 mins) non-A-G (14 mins), and surgeons (18 mins). CONCLUSION: Significant variation in the ADR between endoscopists belonging to different specialties were observed. Although all appear to achieve acceptable ADR (ie at least 25 for men and 15 for women), academic gastroenterologists had better performance than non-academic GI and surgeons. This may be explained by a significantly longer average duration of procedures for the highest ADR group.
RESUMO
Thymosin alpha1 (Talpha1) is a 28 amino acid biologically active protein cleaved from positions 2-29 of a precursor protein, prothymosin alpha. Since its discovery, Talpha1 has been administered to animals and humans in a wide variety of settings and its pharmacologic effects are to enhance cellular immunity. Talpha1 administration is highly effective in settings where irradiation, chemotherapy, tumor burden, or immune senescence have caused a reduction of T cell number and/or function. Recent in vitro studies, including the one reported here, suggest that Talpha1 may act via pathways commonly used by various cytokines. This raises the possibility that Talpha1 and cytokines may have synergistic activity through potentiation of cytokine activity by Talpha1. Improved control of tumor growth when tumor-bearing mice were treated with Talpha1 and high doses of IL-2 has been previously reported. We extended those studies with the Lewis lung carcinoma mouse model using IRX-2, a natural well-defined biologic containing multiple cytokines, in combination with Talpha1 (IRX-3). Although IRX-2 was effective alone (using doses that contain significantly less IL-2 than in most typical studies), adding Talpha1 led to significant improvement in survival of the tumor-bearing mice. Based on these observations, the immunopharmacology of Talpha1 predicts an important clinical role for Talpha1 in the restoration of cellular immune activity when used in combination with cytokines. Patients who experience immune suppression due to the presence of tumor, irradiation, and/or chemotherapy or aging of the host would most benefit from this treatment combination.
Assuntos
Citocinas/farmacologia , Imunidade Celular/efeitos dos fármacos , Timosina/análogos & derivados , Animais , Citocinas/uso terapêutico , Sinergismo Farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Neoplasias Experimentais/tratamento farmacológico , Proteína Quinase C/efeitos dos fármacos , Proteína Quinase C/metabolismo , Timalfasina , Timosina/farmacologia , Timosina/uso terapêuticoRESUMO
African Americans (AA) in the US are twice as likely to be infected with hepatitis C virus (HCV) compared to the non-Hispanic-white US population (Cau). They are also more likely to be infected with HCV genotype 1, more likely to develop hepatocellular carcinoma, and, in addition, have a lower response rate to interferon-based therapies. With the increase in response rates reported for combinations of direct-acting antivirals, the possibility that racial disparity would be eliminated by agents that directly inhibit virus replication has become a reality. The objective of this review is to evaluate the literature from clinical studies and retrospective analysis with respect to the response of AA to the most prescribed antiviral combination sofosbuvir plus ledipasvir. While few studies have focused on AA patients, sufficient information is availed from the literature and studies in our predominately AA clinic population to confirm that ledipasvir-sofosbuvir has a similar effectiveness in AA as compared to Cau.
RESUMO
BACKGROUND: Comparison of teachers' and pupils' definitions of bullying is important for considering the implications for reports of its incidence in schools, for the study of developmental trends in children's and adolescents' perceptions of the phenomenon and for evaluating the effectiveness of interventions designed to combat bullying. AIMS: To investigate the effects of gender, teacher/pupil status and, for pupils, bullied/non-bullied (target/non-target) status and age on the definition of bullying. SAMPLES: Teachers (N=225: 158 women, 67 men) and pupils (N=1,820: 466 boys, 460 girls were 11-12 years old, year 7, and 415 boys, 479 girls were 13-14 years, year 9) in 51 UK secondary schools participated in a questionnaire survey. A total of 557 of the pupils (117 girls and 117 boys aged 11-12 years, and 197 girls and 126 boys aged 13-14 years) reported that they had been bullied at some time in their present school. METHODS: Written questionnaire responses to the question, 'Say what you think bullying is' have been content analysed to derive two sets of categories, one of bullying behaviour and the other of effects of bullying on the target. RESULTS: Regarding both bullying behaviour and the effects of bullying on the target, teachers - by comparison with pupils - have been found to express more comprehensive ideas in their definitions. Specifically, pupils compared with teachers are more likely to restrict their definitions to direct bullying (verbal and/or physical abuse) and are less likely to refer to social exclusion, a power imbalance in the bully's favour and the bully's intention to cause the target hurt or harm and to feel threatened. Analysis of definitions on the bases of sex, pupil age and target/non-target status show that: targets are more likely than non-targets are to refer to the bully's physically and verbally abusive behaviour, and for Year 7 compared with Year 9 pupils, to suggest that bullies socially exclude targets; girls are more likely than boys are to mention verbal abuse and the effects on the target of 'Feels hurt/harm', but boys are more likely than girls are to construe bullying as involving repetition; older pupils are more likely than younger ones are to refer to a power imbalance in the bully's favour but, for bully targets, younger ones compared with older ones are more likely to invoke the idea of social exclusion in their definitions. CONCLUSIONS: The most important implication of the findings of this study that there are important differences between teachers' and pupils' definitions of bullying is that teachers need to listen carefully to what pupils have to say about bullying and work with and help them to develop their conceptions of the phenomenon. Some teachers, too, need to develop their conceptions of bullying.
Assuntos
Atitude , Docentes , Psicologia/estatística & dados numéricos , Transtornos do Comportamento Social , Estudantes , Inquéritos e Questionários , Terminologia como Assunto , Violência , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Variações Dependentes do ObservadorRESUMO
Defining 'effectiveness' in the context of community mental health teams (CMHTs) has become increasingly difficult under the current pattern of provision required in National Health Service mental health services in England. The aim of this study was to establish the characteristics of multi-professional team working effectiveness in adult CMHTs to develop a new measure of CMHT effectiveness. The study was conducted between May and November 2010 and comprised two stages. Stage 1 used a formative evaluative approach based on the Productivity Measurement and Enhancement System to develop the scale with multiple stakeholder groups over a series of qualitative workshops held in various locations across England. Stage 2 analysed responses from a cross-sectional survey of 1500 members in 135 CMHTs from 11 Mental Health Trusts in England to determine the scale's psychometric properties. Based on an analysis of its structural validity and reliability, the resultant 20-item scale demonstrated good psychometric properties and captured one overall latent factor of CMHT effectiveness comprising seven dimensions: improved service user well-being, creative problem-solving, continuous care, inter-team working, respect between professionals, engagement with carers and therapeutic relationships with service users. The scale will be of significant value to CMHTs and healthcare commissioners both nationally and internationally for monitoring, evaluating and improving team functioning in practice.
Assuntos
Serviços Comunitários de Saúde Mental/organização & administração , Transtornos Mentais/terapia , Equipe de Assistência ao Paciente/organização & administração , Inquéritos e Questionários/normas , Comunicação , Continuidade da Assistência ao Paciente/organização & administração , Estudos Transversais , Inglaterra , Humanos , Relações Interprofissionais , Avaliação das Necessidades , Resolução de Problemas , Relações Profissional-Paciente , Psicometria , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Evaluation of advanced fibrosis in patients with hepatitis C virus (HCV) infection is used to facilitate decisions on treatment strategy and to initiate additional screening measures. Unfortunately, most studies have predominately Caucasian (Cau) patients and may not be as relevant for African Americans (AA). AIMS: This study specifically addresses the issue of defining minimal vs. significant fibrosis in African Americans (AA) with chronic hepatitis C (CHC) using noninvasive assays. METHODS: All patients (n = 319) seen between 1 January 2008 and 30 June 2013 for whom a FibroSpect II® (FSII) assay was performed and had data for calculation of aspartate aminotransferase (AST) platelet ratio index (APRI) and Fibrosis-4 (FIB-4) were identified using the medical records. RESULTS: When liver biopsy score and FSII assay results for the AA patients with CHC were compared, 31% of AA had advanced FSII fibrosis scores (F2-F4) despite a biopsy score of F0-F1. In contrast, 10% of Cau over-scored. The AA false positive rate was 14% for APRI and 34% for FIB-4. Combining FSII with either APRI (7% false positive) or FIB-4 (10% false positive) improved the false positive rate in AA to 7% (FSII + APRI) and 10% (FSII + FIB-4) but reduced the sensitivity for significant fibrosis. CONCLUSIONS: The FSII assay overestimates fibrosis in AA and should be used with caution since these patients may not have significant fibrosis. If the APRI or FIB-4 assay is combined with the FSII assay, minimal fibrosis in AA can be defined without subjecting the patients to a subsequent biopsy.
RESUMO
Langerhans cells (LCs) are the antigen-presenting cells of the epithelial layer and are responsible for initiating immune responses against skin and mucosa-invading viruses. Human papillomavirus (HPV)-mediated suppression of LC function is a crucial mechanism of HPV immune evasion, which can lead to persistent infection and development of several human cancers, including cervical, anal, and head and neck cancers. The cell-derived cytokine-based biologic, IRX-2, consists of multiple well-defined cytokines and is broadly active on various immune cell subsets. In this study, we investigated primary human LC activation after exposure to HPV16, followed by treatment with IRX-2 in vitro, and evaluated their subsequent ability to induce HPV16-specific T cells. In contrast to its activity on dendritic cells, HPV16 alone is not sufficient to induce phenotypic and functional activation of LCs. However, IRX-2 induces a significant upregulation of antigen presentation and costimulatory molecules, T helper 1 (Th1)-associated cytokine release, and chemokine-directed migration of LCs pre-exposed to HPV16. Furthermore, LCs treated with IRX-2 after HPV16 exposure induced CD8(+) T-cell responses against specific HLA-A*0201-binding HPV16 T-cell epitopes. The present study suggests that IRX-2 is an attractive immunomodulator for assisting the immune response in eradication of HPV-infected cells, thereby potentially preventing HPV-induced cancers.