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2.
J Behav Med ; 47(3): 355-373, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38017250

RESUMO

Studies show that interpersonal relations impact behavior change. Yet, a comprehensive review of their efficacy remains unclear. This systematic review examines the efficacy of dyadic and group-based studies that intervened on primary endpoints: diet, PA, and weight loss in adults and their networks. We searched five databases for eligible articles published from 1980 to present. Final inclusion and risk of bias were independently determined and agreed upon by two of the paper's co-authors. Nine dyads and twelve group-based studies were eligible. Of the studies, 36% (4/11) of PA studies, 60% (3/5) of diet studies and 57% (8/14) of studies with weight loss as primary outcomes, reported significant findings. Compared to dyadic interventions, a greater proportion of group-based interventions demonstrated efficacy in PA gain and weight loss as outcomes. Approximately 43% of studies demonstrated low to moderate methodological quality. This systematic review synthesized the evidence of dyadic and group studies that intervened on PA, diet, and weight in adults from the same network. Moderately-high risk of bias and lack of diverse representation restricts inferences around efficacy. High-quality rigorous research is needed to understand the efficacy of dyadic and group-based interventions in addressing these co-occurring endpoints of interest.


Assuntos
Dieta , Redução de Peso , Adulto , Humanos , Exercício Físico , Relações Interpessoais
3.
Am J Nurs ; 123(8): 56-61, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37498041

RESUMO

ABSTRACT: Opioid use disorder (OUD) is an important comorbidity to assess and manage in people with cancer. In this article, the authors discuss strategies for safe opioid management in individuals with OUD and cancer-related pain using a composite case example. They highlight core approaches to pain management, including motivational interviewing, harm reduction, and evidence-based treatments, as well as advocacy for person-centered end-of-life care.


Assuntos
Neoplasias , Transtornos Relacionados ao Uso de Opioides , Humanos , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Analgésicos Opioides/uso terapêutico , Manejo da Dor , Comorbidade , Neoplasias/complicações , Neoplasias/tratamento farmacológico
4.
Int J Tuberc Lung Dis ; 27(1): 61-65, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36853123

RESUMO

SETTING: There has been growing recognition on the importance of phenotyping of airway diseases. The eosinophilic phenotype was proposed in bronchiectasis; however, there has not been any evidence on its association with the risk of hospitalised bronchiectasis exacerbations.OBJECTIVE: To investigate the association between baseline blood eosinophil count (BEC) and bronchiectasis exacerbations requiring hospitalisation with validation by an independent cohort.DESIGN: This was a retrospective cohort study.RESULTS: Over a 24-month period, 37/318 (11.6%) study participants experienced an exacerbation requiring hospitalisation. The mean baseline serum eosinophil was 135 ± 92 cells/µL in those who had exacerbations, and 188 ± 161 cells/µL in those who did not. A serum eosinophil level of 250 cells/µL at stable state was the most significant cut-off for predicting hospitalised bronchiectasis exacerbation, which was validated by the independent cohort.CONCLUSIONS: Patients with BEC below 250 cells/µL at stable state are at increased risk of having hospitalised bronchiectasis exacerbations.


Assuntos
Bronquiectasia , Eosinófilos , Humanos , Estudos Retrospectivos , Contagem de Leucócitos , Hospitalização
5.
Ned Tijdschr Tandheelkd ; 130(1): 11-16, 2023 Jan.
Artigo em Holandês | MEDLINE | ID: mdl-36637013

RESUMO

A significant swelling was seen in the floor of the mouth of a newborn girl. The girl could only drink with difficulty. On examination, a soft-elastic swelling was seen beneath the tongue. Ultrasonography and MRI showed a mass located above the hyoid bone. Upon the initial differential diagnosis of a dermoid cyst, an enucleation of the lesion was performed. Histopathological examination suggested a branchiogenic cyst or a digestive duplication cyst. Given the inconclusiveness of additional diagnostic examination, the lesion was diagnosed as a developmental cyst. Six months after enucleation, the infant girl's tongue motility was not restricted and there were no indications of a recurrence. This rare case illustrates the variety in differential diagnosis and the limitations of additional diagnostic examination.


Assuntos
Cisto Dermoide , Neoplasias Bucais , Feminino , Humanos , Recém-Nascido , Cisto Dermoide/diagnóstico , Cisto Dermoide/cirurgia , Cisto Dermoide/patologia , Diagnóstico Diferencial , Soalho Bucal/patologia , Língua/patologia
6.
Int J Oral Maxillofac Surg ; 52(3): 343-352, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35999147

RESUMO

The aim of this study was to compare the effects of maxillomandibular advancement (MMA) on respiratory function between obstructive sleep apnoea (OSA) patients with and without maxillomandibular deficiency, and to compare the changes in facial aesthetics after MMA between the two groups. MMA-treated patients who had both baseline and follow-up polysomnography (PSG) data and lateral cephalograms were enrolled in this retrospective study. In addition to PSG and cephalometric data, patient satisfaction with postoperative breathing and facial aesthetics, and overall satisfaction with the treatment were assessed. Twenty-one patients were classified as not having maxillomandibular deficiency (without-deficiency group) and 40 patients as having maxillomandibular deficiency (with-deficiency group). The improvements in respiratory parameters (e.g., apnoea-hypopnoea index) and patient satisfaction with postoperative breathing were comparable in the two groups (P = 0.094-0.713). The changes in facial profile measurements (e.g., nasal prominence, nasolabial angel, and lip positions relative to the true vertical line) and patient satisfaction with postoperative facial aesthetics were also comparable in the two groups (P = 0.148-0.983). In conclusion, no significant difference in the effects of MMA on respiratory function and facial aesthetics between OSA patients with and without maxillomandibular deficiency was observed.


Assuntos
Avanço Mandibular , Apneia Obstrutiva do Sono , Humanos , Maxila/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Apneia Obstrutiva do Sono/cirurgia , Estética
7.
JBI Evid Synth ; 21(4): 812-825, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36404752

RESUMO

OBJECTIVE: This scoping review aims to describe factors in the existing literature that may inform opioid-prescribing decisions for patients with a past or present history of cancer and past or present substance misuse or substance use disorder. INTRODUCTION: Opioids and opioid-related decisions are critical components of cancer care. Most individuals with cancer will experience pain during cancer care, and over half of patients will receive an opioid prescription. Opioid-prescribing decisions require weighing the benefits and harms. The presence of substance misuse or substance use disorder may elevate the risk of opioid-related harms, but there is a lack of consensus on managing patients at this intersection. INCLUSION CRITERIA: This review will consider studies that include adult patients with a past or present history of cancer who also have pain and current or historical substance misuse or substance use disorder. The pain may be cancer-related or non-cancer-related. Studies of patients with all types of cancer will be eligible for inclusion, with the exception of non-melanoma skin cancers. Eligible studies will explore factors that inform opioid-prescribing decisions in this patient population. METHODS: The review will be conducted according to JBI methodology for scoping reviews. Studies written in English since database inception will be included. The databases to be searched include MEDLINE (Ovid), CINAHL (EBSCO), Embase, APA PsycINFO, and Google Scholar. Eligible studies will undergo data extraction by 2 independent reviewers using a data extraction tool created by the authors. A narrative summary will describe study characteristics, population details, and strategies used to determine appropriate pain management in the patient population.


Assuntos
Neoplasias , Transtornos Relacionados ao Uso de Opioides , Adulto , Humanos , Analgésicos Opioides/efeitos adversos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Dor/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Literatura de Revisão como Assunto
8.
J Palliat Med ; 26(1): 120-130, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36067137

RESUMO

Pain management in palliative care (PC) is becoming more complex as patients survive longer with life-limiting illnesses and population-wide trends involving opioid misuse become more common in serious illness. Buprenorphine, a generally safe partial mu-opioid receptor agonist, has been shown to be effective for both pain management and opioid use disorder. It is critical that PC clinicians become comfortable with indications for its use, strategies for initiation while understanding risks and benefits. This article, written by a team of PC and addiction-trained specialists, including physicians, nurse practitioners, social workers, and a pharmacist, offers 10 tips to demystify buprenorphine use in serious illness.


Assuntos
Buprenorfina , Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Transtornos Relacionados ao Uso de Opioides , Humanos , Buprenorfina/uso terapêutico , Cuidados Paliativos , Analgésicos Opioides/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico
9.
Ned Tijdschr Tandheelkd ; 129(10): 435-441, 2022 Oct.
Artigo em Holandês | MEDLINE | ID: mdl-36222447

RESUMO

A 49-year-old woman who suffered from severe obstructive sleep apnea (OSA) was referred to the department of Oral-, Maxillofacial Surgery department due to progressive limitation of the mouth opening and chronic pain in both temporomandibular joints. Based on clinical and radiological examinations, the patient was diagnosed with recurrent ankylosis of the temporomandibular joints. The patient was treated with 2 patient-specific implants of the temporomandibular joint combined with a Le Fort I osteotomy, and a genioplasty including a genioglossus advancement. This treatment may have advantages for the patient such as a lower recurrence rate of ankylosis, improved maximal mouth opening, pain reduction and improved aesthetic results.


Assuntos
Apneia Obstrutiva do Sono , Transtornos da Articulação Temporomandibular , Anquilose Dental , Feminino , Humanos , Pessoa de Meia-Idade , Osteotomia , Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/diagnóstico , Transtornos da Articulação Temporomandibular/cirurgia
10.
Int J Tuberc Lung Dis ; 26(10): 917-921, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36163658

RESUMO

BACKGROUND Bronchiectasis is a common respiratory disease complicated by periodic exacerbations. The association with different degrees of gastric acid suppression has not been well studied.METHODS A retrospective cohort study of 350 patients was conducted to investigate the association of different gastric acid suppressants with bronchiectasis exacerbation that required hospitalisation. Components of FACED (FEV1% predicted, age, chronic colonisation by Pseudomonas aeruginosa, radiological extent of the disease, and dyspnoea) were adjusted in multivariate analysis.RESULTS Among patients with exacerbation of bronchiectasis, 52 (14.9%) required hospitalisation. Prescription of a high-dose of proton pump inhibitors (PPI) was associated with increased risk of bronchiectasis exacerbation requiring hospitalisation (adjusted OR 2.77, 95% CI 1.01-7.59; P = 0.05). There was no significant association with use of a histamine-2 receptor antagonist (H2RA) (OR 1.28, 95% CI 0.32-5.06) or low-dose PPI (OR 1.47, 95% CI 0.42-5.13). Nonetheless, patients prescribed a high dose of PPI required a significantly longer hospital stay for exacerbation (13.1 ± 1.4 days) than patients not prescribed a gastric acid suppressant (8.2 ± 2.6 days) or those on a low dose PPI (8.3 ± 1.3 days) and H2RA (6.50 ± 1.50 days).CONCLUSIONS Risk of bronchiectasis exacerbation requiring hospitalisation was increased among high-dose PPI users, but not those prescribed an H2RA or low-dose PPI.


Assuntos
Bronquiectasia , Inibidores da Bomba de Prótons , Bronquiectasia/tratamento farmacológico , Histamina , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Hospitalização , Humanos , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos
11.
J Eur Acad Dermatol Venereol ; 36(12): 2414-2422, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35841308

RESUMO

BACKGROUND: Nickel, the fifth most common element on Earth, is the leading inducer of contact allergies in humans, with potent immunological effects. Nickel-induced contact allergies predominantly affect females. Maternal exposure to nickel has been associated with several developmental abnormalities. However, how a maternal nickel exposure affects the development of atopic diathesis and immune abnormalities in children has never been addressed. OBJECTIVES: We aimed to determine whether maternal nickel exposure affects the development of atopic dermatitis and immune abnormalities in their children. METHODS: Using a birth cohort study, we analysed 140 mother-child pairs recruited in 2012-2015 from central Taiwan. Maternal exposure to nickel was estimated using urinary nickel levels measured by inductively coupled plasma mass spectrometry (ICP-MS). The serum levels of 65 analytes and IgE in 3-year-old children were profiled with a multiplex ELISA. The correlation between the maternal urinary nickel concentration and serum analyte levels was assessed using Spearmen's correlation. Multivariant regression analysis was performed to evaluate the association between maternal urinary nickel levels and serum analyte concentrations in their children. RESULTS: The geometric means of the maternal urinary nickel and the children's serum IgE levels were 2.27 µg/L and 69.71 IU/mL, respectively. The maternal nickel exposure was associated with increased serum levels of IL-1ß, IL-2, TNF-α, and leukaemia inhibitory factor (LIF) but with decreased serum levels of matrix metalloproteinase-1 (MMP-1), IL-2R, and eotaxin-1 in the children. In addition, the development of childhood atopic dermatitis at 3 years old was significantly associated with the child's serum levels of IgE and IL-2R, but it was negatively associated with the maternal nickel exposure. CONCLUSIONS: This is the first study showing the potential immunological effects of maternal nickel exposure in their children at an early developmental stage.


Assuntos
Dermatite Atópica , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Humanos , Pré-Escolar , Estudos de Coortes , Níquel/efeitos adversos , Coorte de Nascimento , Imunoglobulina E , Citocinas
12.
Int J Oral Maxillofac Surg ; 51(7): 975-980, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34509364

RESUMO

The aim of this study was to compare two techniques for temporary intraoperative maxillomandibular fixation (TIO-MMF) during orthognathic surgery: steel-wire ligatures versus power chains. Patients undergoing orthognathic surgery between October 2019 and March 2020 were included in a prospective cross-sectional study conducted in three participating hospitals. Data were collected using a standardized measurement form. A total of 44 patients were included, in whom TIO-MMF was applied 79 times. A statistically significant difference in intraoperative loss of stability of the segment relationship was found between steel-wire ligatures (11.4%) and power chains (0%). The mean application time of TIO-MMF differed significantly between steel-wire ligatures (99 seconds) and power chains (157 seconds) (P < 0.001). There was no statistical difference in occurrence of adverse events between the two techniques. This study found that the application of TIO-MMF with power chains is more stable compared to steel-wire ligatures. Steel-wire ligatures were significantly faster to apply, although the absolute difference (less than 1 minute) was small. Other possible advantages of the proposed technique are discussed. The results of this study suggest that power chains for the application of TIO-MMF in orthognathic surgery are a valuable alternative to steel-wire ligatures.


Assuntos
Implantes Dentários , Técnicas de Fixação da Arcada Osseodentária , Estudos Transversais , Humanos , Projetos Piloto , Estudos Prospectivos , Aço
13.
Clin Transl Oncol ; 24(5): 854-863, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34859370

RESUMO

BACKGROUND: Resveratrol, a naturally occurring polyphenolic compound, has been shown to inhibit cancer growth by targeting several cancer-related signalling pathways. In the tumor microenvironment (TME), tumor-associated macrophages (TAMs) are the most abundant leukocyte population that are associated with poor prognosis in over 80% of breast cancer cases. However, little is known about the effect of resveratrol in the TME. METHODS: In this study, MDA-MB-231(MB231), cisplatin resistance MDA-MB-231 (cisR), and T47D were used to examine the antitumor effect of resveratrol. The effectiveness of resveratrol, together with cisplatin as breast cancer treatment was investigated in vivo. Gene expressions of M1 (iNOS and CXCL10) and M2 (ARG1, CD163 and MRC1) markers in differentiated macrophages derived from THP-1 cells were examined to investigate the effect of resveratrol on TAM polarization in breast cancer progression. RESULTS: Our results demonstrated that resveratrol significantly reduced cell proliferation and enhanced chemosensitivity in breast cancer cells by inhibiting production of IL-6 and STAT3 activation. Treatment of resveratrol increased CXCL10 (M1 marker) expression. Further, resveratrol decreased IL-6 levels in LPS-treated differentiated macrophages. The use of resveratrol with cisplatin inhibited suppressed tumor growth when compared with cisplatin alone. CONCLUSION: This study revealed that resveratrol inhibited breast cancer cell proliferation by promoting M1/M2 macrophage polarization ratio and suppressing IL-6/pSTAT3 pathway.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Feminino , Humanos , Interleucina-6/metabolismo , Macrófagos/patologia , Resveratrol/metabolismo , Resveratrol/farmacologia , Microambiente Tumoral
14.
Am J Hosp Palliat Care ; 39(1): 101-107, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33685244

RESUMO

BACKGROUND: The majority of Palliative Care (PC) clinicians report recently caring for a person with a Substance Use Disorder (SUD). The impact of an untreated SUD is associated with significant suffering but many PC clinicians report a lack of confidence in managing this population. OBJECTIVE: This paper aims to demonstrate existing PC skills that can be adapted to provide primary SUD treatment. METHODS: A comprehensive literature review was conducted on quality PC domains and core SUD treatment principles. To demonstrate the shared philosophy and skills of PC clinicians and SUD treatment, the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care and resources outlining core Addiction Medicine and Nursing Competencies were used. RESULTS: There is an abundance of overlapping domains in PC and SUD treatment. This paper focuses on the domains of communication, team-based care, quality of life considerations, addressing social determinants of health, and adherence to ethical principles. In each section, the shared domain in PC and SUD treatment is discussed and steps to expand PC clinician's skills are provided. CONCLUSION: PC clinicians may be among the last healthcare touchpoint for persons with SUD, by naming the shared skills required in PC and evidenced-based SUD treatment, we challenge the field to undertake primary SUD treatment as part of its constant pursuit to better serve people living with serious illness.


Assuntos
Enfermagem de Cuidados Paliativos na Terminalidade da Vida , Transtornos Relacionados ao Uso de Substâncias , Instalações de Saúde , Humanos , Cuidados Paliativos , Qualidade de Vida , Transtornos Relacionados ao Uso de Substâncias/terapia
15.
STAR Protoc ; 3(4): 101919, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36595908

RESUMO

Here, we present a protocol using MATRIX (mass spectrometry analysis of active translation factors using ribosome density fractionation and isotopic labeling experiments) platform to investigate changes of the protein synthesis machinery in U87MG glioblastoma cells in response to the rocaglate silvestrol. This protocol describes steps to perform SILAC (stable isotope labeling by amino acids in cell culture), ribosome density fractionation, protein isolation, and mass spectrometry analysis. This approach can be applied to study any adaptive remodeling of protein synthesis machineries. For complete details on the use and execution of this protocol, please refer to Ho et al. (2021).1.


Assuntos
Glioblastoma , Humanos , Proteômica/métodos , Proteínas/química , Aminoácidos/metabolismo , Espectrometria de Massas/métodos
16.
Cell Rep ; 37(13): 110144, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34965440

RESUMO

Kaposi's sarcoma herpesvirus (KSHV) is an angiogenesis-inducing oncovirus whose ability to usurp the oxygen-sensing machinery is central to its oncogenicity. By upregulating the hypoxia-inducible factors (HIFs), KSHV reprograms infected cells to a hypoxia-like state, triggering angiogenesis. Here we identify a link between KSHV replicative biology and oncogenicity by showing that KSHV's ability to regulate HIF2α levels and localization to the endoplasmic reticulum (ER) in normoxia enables translation of viral lytic mRNAs through the HIF2α-regulated eIF4E2 translation-initiation complex. This mechanism of translation in infected cells is critical for lytic protein synthesis and contributes to KSHV-induced PDGFRA activation and VEGF secretion. Thus, KSHV regulation of the oxygen-sensing machinery allows virally infected cells to initiate translation via the mTOR-dependent eIF4E1 or the HIF2α-dependent, mTOR-independent, eIF4E2. This "translation initiation plasticity" (TRIP) is an oncoviral strategy used to optimize viral protein expression that links molecular strategies of viral replication to angiogenicity and oncogenesis.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinogênese/patologia , Herpesvirus Humano 8/fisiologia , Hipóxia/fisiopatologia , Iniciação Traducional da Cadeia Peptídica , Sarcoma de Kaposi/patologia , Replicação Viral , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Carcinogênese/genética , Carcinogênese/metabolismo , Fator de Iniciação 4E em Eucariotos/genética , Fator de Iniciação 4E em Eucariotos/metabolismo , Humanos , Sarcoma de Kaposi/genética , Sarcoma de Kaposi/metabolismo , Sarcoma de Kaposi/virologia , Ativação Viral
17.
Nutrients ; 13(11)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34836025

RESUMO

Diabetic peripheral neuropathy (DPN) is the most common microvascular complication of diabetes that affects approximately half of the diabetic population. Up to 53% of DPN patients experience neuropathic pain, which leads to a reduction in the quality of life and work productivity. Tocotrienols have been shown to possess antioxidant, anti-inflammatory, and neuroprotective properties in preclinical and clinical studies. This study aimed to investigate the effects of tocotrienol-rich vitamin E (Tocovid SuprabioTM) on nerve conduction parameters and serum biomarkers among patients with type 2 diabetes mellitus (T2DM). A total of 88 patients were randomized to receive 200 mg of Tocovid twice daily, or a matching placebo for 12 months. Fasting blood samples were collected for measurements of HbA1c, renal profile, lipid profile, and biomarkers. A nerve conduction study (NCS) was performed on all patients at baseline and subsequently at 2, 6, 12 months. Patients were reassessed after 6 months of washout. After 12 months of supplementation, patients in the Tocovid group exhibited highly significant improvements in conduction velocity (CV) of both median and sural sensory nerves as compared to those in the placebo group. The between-intervention-group differences (treatment effects) in CV were 1.60 m/s (95% CI: 0.70, 2.40) for the median nerve and 2.10 m/s (95% CI: 1.50, 2.90) for the sural nerve. A significant difference in peak velocity (PV) was also observed in the sural nerve (2.10 m/s; 95% CI: 1.00, 3.20) after 12 months. Significant improvements in CV were only observed up to 6 months in the tibial motor nerve, 1.30 m/s (95% CI: 0.60, 2.20). There were no significant changes in serum biomarkers, transforming growth factor beta-1 (TGFß-1), or vascular endothelial growth factor A (VEGF-A). After 6 months of washout, there were no significant differences from baseline between groups in nerve conduction parameters of all three nerves. Tocovid at 400 mg/day significantly improve tibial motor nerve CV up to 6 months, but median and sural sensory nerve CV in up to 12 months of supplementation. All improvements diminished after 6 months of washout.


Assuntos
Neuropatias Diabéticas/terapia , Suplementos Nutricionais , Condução Nervosa/efeitos dos fármacos , Tocotrienóis/administração & dosagem , Vitamina E/administração & dosagem , Idoso , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Nervo Mediano/efeitos dos fármacos , Pessoa de Meia-Idade , Neurônios Motores/efeitos dos fármacos , Nervo Sural/efeitos dos fármacos , Tíbia/inervação , Fator de Crescimento Transformador beta1/sangue , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/sangue
18.
Cell Rep ; 37(2): 109806, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34644561

RESUMO

Tactical disruption of protein synthesis is an attractive therapeutic strategy, with the first-in-class eIF4A-targeting compound zotatifin in clinical evaluation for cancer and COVID-19. The full cellular impact and mechanisms of these potent molecules are undefined at a proteomic level. Here, we report mass spectrometry analysis of translational reprogramming by rocaglates, cap-dependent initiation disruptors that include zotatifin. We find effects to be far more complex than simple "translational inhibition" as currently defined. Translatome analysis by TMT-pSILAC (tandem mass tag-pulse stable isotope labeling with amino acids in cell culture mass spectrometry) reveals myriad upregulated proteins that drive hitherto unrecognized cytotoxic mechanisms, including GEF-H1-mediated anti-survival RHOA/JNK activation. Surprisingly, these responses are not replicated by eIF4A silencing, indicating a broader translational adaptation than currently understood. Translation machinery analysis by MATRIX (mass spectrometry analysis of active translation factors using ribosome density fractionation and isotopic labeling experiments) identifies rocaglate-specific dependence on specific translation factors including eEF1ε1 that drive translatome remodeling. Our proteome-level interrogation reveals that the complete cellular response to these historical "translation inhibitors" is mediated by comprehensive translational landscape remodeling.


Assuntos
Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , Animais , Benzofuranos/farmacologia , Linhagem Celular Tumoral , Fator de Iniciação 4A em Eucariotos/efeitos dos fármacos , Fator de Iniciação 4A em Eucariotos/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Cultura Primária de Células , Biossíntese de Proteínas/fisiologia , Proteômica/métodos , Ribossomos/metabolismo , Transcriptoma/efeitos dos fármacos , Transcriptoma/genética , Triterpenos/farmacologia
19.
Ned Tijdschr Tandheelkd ; 128(9): 429-433, 2021 Sep.
Artigo em Holandês | MEDLINE | ID: mdl-34490767

RESUMO

A 41-year-old woman, who was referred with a reddish purple like lesion on the left side of the tongue, appeared to have an angiokeratoma after histopathological examination. Because of the benign character of this lesion and the absence of any complaints, no adjuvant treatment after excisional biopsy was indicated. Angiokeratomas rarely appear as solitary oral lesions. More often they are seen as part of an underlying systemic disease, mostly Fabry disease. Due to widespread skin involvement of angiokeratomas with Fabry disease, referral to a dermatologist is indicated when oral lesions are encountered. Esthetically unpleasing or painful angiokeratomas can be locally excised or treated by laser- or cryotherapy.


Assuntos
Angioceratoma , Neoplasias Cutâneas , Adulto , Angioceratoma/diagnóstico , Biópsia , Feminino , Humanos , Neoplasias Cutâneas/diagnóstico , Língua
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