RESUMEN
PURPOSE OF REVIEW: It is essential to have validated and reliable pain measurement tools that cover a wide range of areas and are tailored to individual patients to ensure effective pain management. The main objective of this review is to provide comprehensive information on commonly used pain scales and questionnaires, including their usefulness, intended purpose, applicability to different patient populations, and associated advantages and disadvantages. RECENT FINDINGS: Acute pain questionnaires typically focus on measuring the severity of pain and the extent of relief achieved through interventions. Chronic pain questionnaires evaluate additional aspects such as pain-related functional limitations, psychological distress, and psychological well-being. The selection of an appropriate pain scale depends on the specific assessment objectives. Additionally, each pain scale has its strengths and limitations. Understanding the differences among these pain scales is essential for selecting the most appropriate tool tailored to individual patient needs in different settings. CONCLUSION: Medical professionals encounter challenges in accurately assessing pain. Physicians must be familiar with the different pain scales and their applicability to specific patient population.
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Dolor Agudo , Dolor Crónico , Humanos , Dimensión del Dolor , Dolor Crónico/diagnóstico , Dolor Crónico/terapia , Dolor Crónico/psicología , Encuestas y Cuestionarios , Manejo del Dolor , Evaluación de la DiscapacidadRESUMEN
PURPOSE OF REVIEW: Inadequate pain relief after cardiac surgery results in decreased patient experience and satisfaction, increased opioid consumption with its associated adverse consequences, and reduced efficiency metrics. To mitigate this, regional analgesic techniques are an increasingly important part of the perioperative cardiac anesthesia care plan. The purpose of this review is to compare current regional anesthesia techniques, and the relative evidence supporting their efficacy and safety in cardiac surgery. RECENT FINDINGS: Numerous novel plane blocks have been developed in recent years, with evidence of improved pain control after cardiac surgery. SUMMARY: The current data supports the use of a variety of different regional anesthesia techniques to reduce acute pain after cardiac surgery. However, future randomized trials are needed to quantify and compare the efficacy and safety of different regional techniques for pain control after cardiac surgery.
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Anestesia de Conducción , Procedimientos Quirúrgicos Cardíacos , Anestesia de Conducción/efectos adversos , Anestesia de Conducción/métodos , Anestesia Local , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Humanos , Manejo del Dolor/métodos , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & controlRESUMEN
PURPOSE OF REVIEW: The purpose of this review is to examine the impact of smoking and its role on the development of chronic pain and provide a critical review of recent literature. RECENT FINDINGS: Recent studies demonstrate the bidirectional and dependent relationship between smoking and chronic pain. Those who are in pain have a more difficult time in the cessation of smoking as well as an increased sensitivity to pain during abstinence, lower confidence, and higher relapse rates. The fear of pain and the anxiety and depression that abstinence causes results in a grim outcome for long-term cessation. The dependent nature between chronic pain and smoking is affected by numerous variables. Providers should consider a multiprong approach to treating chronic pain and targeting smoking cessation treatment by providing motivational therapy, nicotine replacement, and medication therapies to prevent relapse, and providing those who are more likely to relapse with a higher level of care.
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Dolor Crónico , Cese del Hábito de Fumar , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/terapia , Humanos , Nicotina/efectos adversos , Recurrencia , Fumar/efectos adversos , Fumar/tratamiento farmacológico , Cese del Hábito de Fumar/métodos , Dispositivos para Dejar de Fumar TabacoRESUMEN
Chronic liver disease and hepatocellular carcinoma (HCC) are life-threatening diseases with limited treatment options. The lack of clinically relevant/tractable experimental models hampers therapeutic discovery. Here, we develop a simple and robust human liver cell-based system modeling a clinical prognostic liver signature (PLS) predicting long-term liver disease progression toward HCC. Using the PLS as a readout, followed by validation in nonalcoholic steatohepatitis/fibrosis/HCC animal models and patient-derived liver spheroids, we identify nizatidine, a histamine receptor H2 (HRH2) blocker, for treatment of advanced liver disease and HCC chemoprevention. Moreover, perturbation studies combined with single cell RNA-Seq analyses of patient liver tissues uncover hepatocytes and HRH2+, CLEC5Ahigh, MARCOlow liver macrophages as potential nizatidine targets. The PLS model combined with single cell RNA-Seq of patient tissues enables discovery of urgently needed targets and therapeutics for treatment of advanced liver disease and cancer prevention.
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Descubrimiento de Drogas , Hígado/patología , Modelos Biológicos , Animales , Carcinogénesis/patología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Quimioprevención , Estudios de Cohortes , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HEK293 , Hepacivirus/fisiología , Hepatitis C/genética , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Hepatocitos/patología , Humanos , Vigilancia Inmunológica/efectos de los fármacos , Inflamación/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/patología , Neoplasias Hepáticas/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones Noqueados , Nizatidina/farmacología , Pronóstico , Transducción de Señal/efectos de los fármacos , Transcriptoma/genéticaRESUMEN
Hepatocellular carcinoma (HCC) is a highly morbid condition with lack of effective treatment options. HCC arises from chronically inflamed and damaged liver tissue; therefore, chemoprevention may be a useful strategy to reduce HCC incidence. Several reports suggest that epigallocatechin gallate (EGCG), extracted from green tea, can suppress liver inflammation and fibrosis in animal models, but its role in HCC chemoprevention is not well established. In this study, male Wistar rats were injected with diethylnitrosamine at 50 mg/kg for 18 weeks to induce cirrhosis and HCC, and EGCG was given in drinking water at a concentration of 0.02%. Clinically achievable dosing of EGCG was well-tolerated in diethylnitrosamine-injured rats and was associated with improved serum liver markers including alanine transaminase, aspartate transaminase, and total bilirubin, and reduced HCC tumor formation. Transcriptomic analysis of diethylnitrosamine-injured hepatic tissue was notable for increased expression of genes associated with the Hoshida high risk HCC gene signature, which was prevented with EGCG treatment. EGCG treatment also inhibited fibrosis progression, which was associated with inactivation of hepatic stellate cells and induction of the senescence-associated secretory phenotype. In conclusion, EGCG administered at clinically safe doses exhibited both chemopreventive and antifibrotic effects in a rat diethylnitrosamine liver injury model.
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Anticarcinógenos/uso terapéutico , Carcinoma Hepatocelular/prevención & control , Catequina/análogos & derivados , Senescencia Celular/efectos de los fármacos , Células Estrelladas Hepáticas/efectos de los fármacos , Neoplasias Hepáticas Experimentales/prevención & control , Animales , Anticarcinógenos/farmacología , Biomarcadores , Carcinoma Hepatocelular/inducido químicamente , Catequina/farmacología , Catequina/uso terapéutico , Dietilnitrosamina , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/inducido químicamente , Masculino , Fenotipo , Lesiones Precancerosas/inducido químicamente , Ratas , Té/química , TranscriptomaRESUMEN
Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer (PC). Focused loss-of-function genetic screen of top-upregulated Nups in aggressive PC models identified POM121 as a key contributor to PC aggressiveness. Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models. Our studies molecularly establish a role of NPCs in PC progression and give a rationale for NPC-regulated nuclear import targeting as a therapeutic strategy for lethal PC. These findings may have implications for understanding how NPC deregulation contributes to the pathogenesis of other tumor types.
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Factor de Transcripción E2F1/metabolismo , Glicoproteínas de Membrana/metabolismo , Poro Nuclear/fisiología , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Factores de Transcripción/metabolismo , Transporte Activo de Núcleo Celular , Carcinogénesis , Núcleo Celular/metabolismo , Proliferación Celular , Factor de Transcripción GATA2/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Membrana Nuclear , Proteínas de Complejo Poro Nuclear , Transducción de SeñalRESUMEN
Evidence of male-to-female sexual transmission of Zika virus (ZIKV) and viral RNA in semen and sperm months after infection supports a potential role for testicular cells in ZIKV propagation. Here, we demonstrate that germ cells (GCs) are most susceptible to ZIKV. We found that only GCs infected by ZIKV, but not those infected by dengue virus and yellow fever virus, produce high levels of infectious virus. This observation coincides with decreased expression of interferon-stimulated gene Ifi44l in ZIKV-infected GCs, and overexpression of Ifi44l results in reduced ZIKV production. Using primary human testicular tissue, we demonstrate that human GCs are also permissive for ZIKV infection and production. Finally, we identified berberine chloride as a potent inhibitor of ZIKV infection in both murine and human testes. Together, these studies identify a potential cellular source for propagation of ZIKV in testes and a candidate drug for preventing sexual transmission of ZIKV.
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Antivirales/farmacología , Berberina/farmacología , ARN Viral/análisis , Enfermedades Virales de Transmisión Sexual/prevención & control , Espermatozoides/virología , Testículo/virología , Replicación Viral/efectos de los fármacos , Infección por el Virus Zika/transmisión , Virus Zika/crecimiento & desarrollo , Animales , Antígenos/biosíntesis , Proliferación Celular , Células Cultivadas , Chlorocebus aethiops , Proteínas del Citoesqueleto/biosíntesis , Virus del Dengue/crecimiento & desarrollo , Humanos , Interferón Tipo I/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , ARN Viral/aislamiento & purificación , Receptor de Interferón alfa y beta/genética , Enfermedades Virales de Transmisión Sexual/virología , Testículo/citología , Células Vero , Replicación Viral/fisiología , Virus de la Fiebre Amarilla/crecimiento & desarrollo , Virus Zika/aislamiento & purificación , Infección por el Virus Zika/virologíaRESUMEN
Autophagy and the unfolded protein response (UPR) both promote activation of hepatic stellate cells (HSC), however the link between the two stimuli remains unclear. Here we have explored the role of X-box binding protein 1 (XBP1), one of three UPR effector pathways and sought to establish the interdependence between autophagy and the UPR during HSC activation. XBP1 induction accompanied both culture-based HSC activation and ER stress induced by tunicamycin. Ectopic overexpression of XBP1 induced collagen 1-alpha expression in HSCs, which was inhibited by knockdown of ATG7, a critical autophagy mediator. Genome-wide transcriptomic profiling indicated an upregulation of collagen synthesis pathways, but not of the transforming growth factor (TGF)-b pathway, a canonical fibrogenic driver, suggesting that XBP1 activates a specific subset of fibrogenesis pathways independent of TGF-ß1. XBP1 target gene signatures were significantly induced in rodent liver fibrosis models (n = 3-5) and in human samples of non-alcoholic fatty liver disease (NAFLD) (n = 72-135). Thus, XBP1-mediated UPR contributes to fibrogenic HSC activation and is functionally linked to cellular autophagy.
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Autofagia/fisiología , Células Estrelladas Hepáticas/metabolismo , Enfermedad del Hígado Graso no Alcohólico/patología , Respuesta de Proteína Desplegada/fisiología , Proteína 1 de Unión a la X-Box/metabolismo , Animales , Proteína 7 Relacionada con la Autofagia/genética , Línea Celular , Colágeno Tipo I/biosíntesis , Estrés del Retículo Endoplásmico/efectos de los fármacos , Células HEK293 , Humanos , Cirrosis Hepática/patología , Ratones , Ratones Endogámicos C57BL , Interferencia de ARN , ARN Interferente Pequeño , Tunicamicina/efectos adversos , Proteína 1 de Unión a la X-Box/genéticaRESUMEN
Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/prevención & control , Perfilación de la Expresión Génica/métodos , Cirrosis Hepática/genética , Neoplasias Hepáticas/prevención & control , Lisofosfolípidos/biosíntesis , Animales , Antineoplásicos/farmacología , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Redes Reguladoras de Genes , Predisposición Genética a la Enfermedad , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/genética , Ratas , Factores de Riesgo , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Drug development has been a costly and lengthy process with an extremely low success rate and lack of consideration of individual diversity in drug response and toxicity. Over the past decade, an alternative "big data" approach has been expanding at an unprecedented pace based on the development of electronic databases of chemical substances, disease gene/protein targets, functional readouts, and clinical information covering inter-individual genetic variations and toxicities. This paradigm shift has enabled systematic, high-throughput, and accelerated identification of novel drugs or repurposed indications of existing drugs for pathogenic molecular aberrations specifically present in each individual patient. The exploding interest from the information technology and direct-to-consumer genetic testing industries has been further facilitating the use of big data to achieve personalized Precision Medicine. Here we overview currently available resources and discuss future prospects.