Добірка наукової літератури з теми "Wonga Park (Vic )"

Em 2003, a Organização Mundial de Colégios Nacionais, Academias e Associações Acadêmicas de Médicos gerais/Médicos de Família (WONCA) propôs um conceito relativamente pouco discutido que visa proteger os pacientes da intervenção médica desnecessária e prevenir iatrogenias: a prevenção quaternária. Tal conceito tem evidente relevância para a saúde pública e para o Sistema Único de Saúde (SUS), em tempos de intensa medicalização social e expansão da atenção à saúde via Estratégia Saúde da Família. Neste artigo, o conceito de prevenção quaternária é apresentado e contextualizado, e sua relevância é discutida, ressaltando três situações comuns do cuidado médico geradoras de grande iatrogenia: excesso de rastreamento, de solicitação de exames complementares e de medicalização de fatores de risco. Defende-se a necessidade da adoção e discussão deste conceito no SUS e especialmente na atenção primária à saúde.

Abstract Extracted from the root tuber of Ophiopogon japonicas, ophiopogon is well known to have an anti-cancer effect. However, the underlying mechanisms are still largely unknown. Here, we report that Ophiopogon D (OP-D) can inhibit colon cancer cell proliferation and induce apoptosis by inhibiting c-Myc expression through activation of p53 and CNOT2 regulation. Our results showed that OP-D induced p53 expression via ribosomal protein L5 or L11 and inhibited c-Myc expression through CNOT2 in a dose-dependent manner. Additionally, OP-D regulated cyclin D1 and CDK4 which are well known as cell cycle regulatory proteins. Consistently, OP-D inhibited the phosphorylation of AKT expression in a dose-dependent manner. Furthermore, OP-D shortened c-Myc’s half-life in a time-dependent manner. Furthermore, CNOT2 knockdown enhanced the inhibitory effect of OP-D on c-Myc in colon cancer cells. Interestingly, OP-D has increased the apoptotic effect of colon cancer cells when combined with doxorubicin or 5-FU, a treatment already used clinically. Altogether, our results suggested that OP-D regulates colon cancer cell survival and induces apoptosis by inhibiting c-Myc expression via activation of p53 and CNOT2 regulation. Citation Format: Hyun Min Ko, Wona Jee, Do-il Park, Somi Park, Ye-Rin Park, Hyeung-Jin Jang, Ji Hoon Jung. Ophiopogonin D increase apoptosis by activating p53 via ribosomal protein L5 and L11 and inhibiting the expression of c-Myc via CNOT2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 864.

A necessidade de um processo de especialização em larga escala em Medicina de Família e Comunidade (MFC) para os médicos da Estratégia Saúde da Família no Brasil (ESF) é identificada nesse documento. Os programas de residência médica (PRMs) seguem como padrão-ouro de especialização, mas não são suficientes para atingir o objetivo acima. Estimula-se que o processo seja acreditado pela Sociedade Brasileira de Medicina de Família e Comunidade (SBMFC) e que seus concluintes sejam certificados por meio do concurso de titulação TEMFC. Modalidades à distância com momentos presenciais são as mais adequadas, observando-se propiciar acesso a profissionais já inseridos em serviço, valorizar sua continuidade nos mesmos, orientar o aprendizado para uma integralidade inteligente e coordenar diferentes recursos para viabilizar o ensino-aprendizagem. As competências buscadas são as definidas pela WONCA, adaptadas à realidade nacional. Aprender a aprender como um MFC é o principal objetivo visado. Casos complexos,construídos de acordo com uma matriz de agravos e problemas diversos, atendidas às realidades regionais, são a principal ferramenta do processo. A SBMFC propõe-se a impulsionar tal estratégia

Abstract Targeted protein degradation (TPD) molecules, including IMiD-based molecular glues and heterobifunctional degraders have expanded the breadth of therapeutic options through both their catalytic mechanism of action and ability to degrade previously “undruggable” target proteins. To increase the efficacy vs. tolerability window of protein degradation and improve drug delivery we combine the catalytic approach of targeted protein degradation with the precision of tumor targeting therapeutic antibodies. Here, we describe the development of ORM-5029, a highly potent and selective GSPT1 degrader targeting HER2-expressing tumor cells. We first screened a panel of cell lines to identify tumors where treatment with a selective, membrane-permeable, molecular glue (SMol007) would exhibit the most potent GSPT1 degradation, integrated stress response, and ultimately apoptosis. HER2+ breast cancer cell lines were more sensitive to GSPT1 degradation than the average IC50 for all cell lines tested. Several of our GSPT1 degrader molecules were tested in HER2-positive tumor models and displayed a consistent pattern of potent cytotoxicity. An unbiased global proteomics evaluation of changes in abundance identified SMol006 as a specific GSPT1 degrader, with no significant depletion of over 6500 other proteins detected. To evaluate whether antibody delivery could provide a potency increase of Smol006 and other GSTP1 degrader payloads, we conjugated these payloads to the HER2-targeting antibodies, trastuzumab and pertuzumab. Given the comparable activity of both antibodies and frequent use of trastuzumab as the antibody domain of several ADCs, we selected pertuzumab as our targeting antibody. Further medicinal chemistry optimization and evaluation of many linker-payloads led to the identification of our first preclinical AnDC candidate ORM-5029, which is composed of SMol006, a highly-potent GSPT1 degrader conjugated to pertuzumab via a clinically-validated Val-Cit PABc linker. ORM-5029 treatment in the HER2-expressing cell lines showed 10-1000 fold superiority in potency compared to SMol006, Kadcyla and/or Enhertu treatment. We evaluated ORM-5029 in several in vivo xenograft models and observed robust efficacy, following a single-dose treatment testing as low as 3 mg/kg. In the BT474 xenograft model, treatment with ORM-5029 demonstrated single-dose activity superior to Kadcyla, and comparable to Enhertu when given at an equivalent dose. In an HCC1569 xenograft model, tumor growth inhibition correlated with the degree and duration of GSPT1 depletion and changes in expression of previously described integrated stress response biomarker genes. ORM-5029 is currently in preclinical development as a potential first-in-class targeted protein degrader therapy with HER2-targeted delivery. Citation Format: James Palacino, Chen Bai, Yong Yi, Anna Skaletskaya, Khuloud Takrouri, Wesley Wong, Min-Soo Kim, Dong-Ki Choi, Da-Young Kim, Yeonhee Yang, Jiae Kook, Pedro Lee, Hangyeol Jeong, Sang-Mi Jee, Jiyun Park, Ki-Hwan Chang, Nathan Fishkin, Peter U. Park. ORM-5029: A first-in-class targeted protein degradation therapy using antibody neodegrader conjugate (AnDC) for HER2-expressing breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3933.

Abstract BACKGROUND: Autologous stem cell transplantation (ASCT) for multiple myeloma (MM) entails sudden life changes including acute symptom burden, changes in physical function, and shifting caregiver dynamics. Several studies have shown that anxiety, insomnia, and distress rise in the initial weeks following ASCT before slowly recovering. Long-term consequences of these acute exacerbations include persistent quality of life (QOL) impairments (El-Jawahri 2016), post-traumatic stress disorder (Griffith 2020), and the usage of potentially inappropriate medications (PIMs) for symptom management (Banerjee 2021). We have recently completed a pilot study of digital life coaching (DLC), whereby life coaches work with patients via phone calls and text messages to provide longitudinal support, education, and accountability to meet wellbeing-related goals. Our pilot study of 15 patients demonstrated the feasibility of DLC during this period, with bidirectional patient-coach engagement occurring every 5-7 days even during index hospitalizations for ASCT (Banerjee 2021). Based on these positive results, we have now launched a randomized Phase 2 study of DLC versus usual care among patients with MM undergoing ASCT. STUDY DESIGN: Our study is registered at clinicaltrials.gov as NCT04589286. We plan to enroll 60 adult patients with MM undergoing first ASCT at our institution. Inclusion criteria include English language proficiency and ownership of a personal cellphone. However, neither smartphones nor specific mobile apps are required for study participation. All patients, including those in the control arm, receive brief wellness-related tips with each request for PRO data as outlined below. As shown in the Figure, patients in the DLC arm are paired with a trained life coach beginning at Day -10 before ASCT. Coaches use structured frameworks to assist patients longitudinally with identifying and accomplishing wellbeing-related goals. Specific coaching topics can vary from week to week and are set by each patient. In addition to weekly coach-led phone calls, patients are encouraged to maintain bidirectional communication via phone/text/email as often as desired. Patients in the control arm do not receive access to DLC. Our primary endpoint is the total usage of sedative-class PIMs - including lorazepam, temazepam, zolpidem, and other similar medications - prescribed for anxiety or insomnia during each of 4 four-week study subperiods identified in the Figure. Secondary endpoints include patient-reported outcome (PRO) assessments of QOL (PROMIS Global Health), distress (NCCN Distress Thermometer), and insomnia (PROMIS Sleep Disturbances 4A). PRO assessments are collected exclusively using automated REDCap emails every 1-2 weeks as shown in the Figure. PROGRESS TO DATE: As of the data cutoff (7/31/21), 19 patients have enrolled onto our study and 5 have completed all follow-up. The median age of enrolled patients is 62 (range: 31-77), with 26% of patients aged 70 or older. As shown in our pilot study (Banerjee 2021), PRO collection via automated REDCap emails is feasible. Specifically, of 93 email-based requests for PRO assessments as of the data cutoff, 92 (99%) have been completed. Analyses of PRO assessment responses and PIM usage will be conducted after study completion. DISCUSSION: Improving patient wellbeing during the acute peri-ASCT period is an unmet need in multiple myeloma. Published supportive strategies during this time include music therapy (Bates 2017), acupuncture (Deng 2018), palliative care (El-Jawahri 2017), and programmed hospital room lighting (Valdimarsdottir 2018). DLC may offer unique advantages given its easy accessibility and unified patient-facing interface across hospital/clinic/home transitions. These strengths may be particularly relevant in light of the COVID-19 pandemic, where home-based follow-up after ASCT has become more common. That being said, broadening the accessibility of DLC to include patients with limited English proficiency or patients without personal cell phones are important priorities for future studies. In summary, our randomized Phase 2 study of DLC versus usual care is ongoing. If shown to reduce PIM prescription rates while improving wellbeing-related PRO trajectories longitudinally, DLC may become a standard of care for patients with hematologic malignancies undergoing ASCT. Figure 1 Figure 1. Disclosures Banerjee: Pack Health: Research Funding; SparkCures: Consultancy; Sanofi: Consultancy. Knoche: Amgen: Honoraria. Brassil: Abbvie: Research Funding; Astellas: Research Funding; BMS: Research Funding; Daiichi Sankyo: Research Funding; Genentech: Research Funding; GSK: Research Funding; Sanofi: Research Funding; Pack Health: Current Employment. Jackson: Pack Health: Current Employment. Patel: Pack Health: Current Employment. Lo: Oncopeptides: Consultancy; EUSA Pharma: Consultancy. Chung: Caelum: Research Funding. Wong: Amgen: Consultancy; Genentech: Research Funding; Fortis: Research Funding; Janssen: Research Funding; GloxoSmithKlein: Research Funding; Dren Biosciences: Consultancy; Caelum: Research Funding; BMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Wolf: Adaptive Biotechnologies: Consultancy; Teneobio: Consultancy; Sanofi: Consultancy; Amgen: Consultancy. Martin: Oncopeptides: Consultancy; Sanofi: Research Funding; Amgen: Research Funding; Janssen: Research Funding; GlaxoSmithKline: Consultancy. Shah: Bluebird Bio: Research Funding; GSK: Consultancy; Janssen: Research Funding; Indapta Therapeutics: Consultancy; BMS/Celgene: Research Funding; CareDx: Consultancy; CSL Behring: Consultancy; Kite: Consultancy; Nektar: Research Funding; Karyopharm: Consultancy; Amgen: Consultancy; Oncopeptides: Consultancy; Poseida: Research Funding; Precision Biosciences: Research Funding; Sanofi: Consultancy; Sutro Biopharma: Research Funding; Teneobio: Research Funding.

Introdução: As alterações vasculares são anomalias de desenvolvimento dos vasos que proporcionam acúmulo de sangue e são de etiologia desconhecida. Fazem parte deste grupo de lesões as malformações arteriovenosas, hemangiomas, linfoangiomas e varicosidades. Embora não raras, as lesões vasculares que ocorrem nos lábios, por vezes, interferem na estética e apresentam dificuldades quanto ao seu diagnóstico e tratamento. Objetivo: Descrever um caso clínico realizado com laser de diodo de alta potência para a fotocoagulação de uma lesão vascular, abordando suas vantagens e limitações em comparação ao tratamento cirúrgico. Material e Método: O procedimento foi realizado em um paciente de 53 anos, sexo feminino, branca, com queixa de aparecimento de uma bolha de sangue no lábio com evolução de aproximadamente oito anos. Ao exame físico intraoral, observou-se nódulo em vermelhão do lábio inferior, do lado direito, próxima à comissura labial, medindo aproximadamente 1,0 cm de diâmetro, de base séssil, superfície lisa, limites bem definidos, coloração violácea, consistência macia e sem sintomatologia dolorosa à palpação. Após a diascopia e diagnóstico clínico de lesão vascular, optou-se pela fotocoalulação com laser de diodo de alta potência. Resultados: Houve regressão total da lesão, após uma única aplicação, sem complicações trans e pós-operatórias, sem sangramento durante a cirurgia, o que proporcionou melhor visão do campo operatório e resultou em um procedimento minimamente invasivo. A paciente encontra-se em proservação, sem recidiva da lesão. Conclusão: A fotocoagulação pode ser considerada como uma alternativa segura e eficiente para o tratamento de lesões vasculares. Descritores: Lesões do Sistema Vascular; Fotocoagulação; Laser; Mucosa Bucal. 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Abstract BACKGROUND: The operationalization of chimeric antigen receptor (CAR-T) therapy for hematologic malignancies can be complex for patients and their caregivers. In the weeks before CAR-T therapy, patients must process large amounts of information and coordinate logistics involving caregivers, lodging, and transportation. Immediately following CAR-T therapy, patients must be monitored closely for toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). In the months following CAR-T therapy, patients may be referred back to local oncologists without a clear plan for managing potential late effects such as hypogammaglobulinemia or neuropsychiatric complications (Chakraborty 2021). Mobile health (mHealth) apps may be able to improve the patient experience during CAR-T therapy by facilitating care coordination, home-based toxicity monitoring, and patient education (Banerjee 2021). By empowering patients and caregivers to better understand CAR-T therapy and actively participate in their care, mHealth tools may ultimately augment workflows for CAR-T clinics as well. However, the feasibility and acceptability of such supportive mHealth apps during CAR-T therapy have not been established. STUDY DESIGN: We have designed a "Companion for CAR-T" mHealth app to assist with care coordination, toxicity monitoring, and patient education during CAR-T therapy. Key components of the app are summarized in the Figure. In brief, pre-CAR-T components include educational videos and dynamic calendars to assist patients with coordinating logistics. Post-CAR-T components include app-based prompts to input body temperature daily, an electronic Immune Effector Cell-Associated Encephalopathy (eICE) screening tool for ICANS that can be administered by caregivers, and a patient-specific long-term survivorship care plan. Global app components include an 'Appointment Companion' to facilitate patient-provider discussions during appointments as well as a digital CAR-T wallet card to convey key health-related information to other healthcare providers. We plan to investigate the "Companion for CAR-T" app through a pilot study of 20 patients receiving commercially available CAR-T therapies for any hematologic malignancy at our institution. Co-primary endpoints include (1) app feasibility, defined as the percentage of patients who access all 5 core modules shown in the Figure at least once; and (2) app acceptability, defined as the percentage of patients who agree that the app was helpful during their experience with CAR-T therapy. Secondary endpoints include the incidence of fevers or eICE deficits recorded via the app. Exploratory endpoints include longitudinal trends in patient-reported outcomes such as emotional distress at each clinic visit. DISCUSSION: If feasibility and acceptability of the "Companion for CAR-T" app are demonstrated through this pilot study, we plan to launch a multicenter randomized Phase 2 study of this mHealth tool versus usual care to assess its effect on perceived stress and decisional conflict. Other important steps for our group include the translation of app content into different languages and the provision of tablet computing devices for patients who do not own smartphones. Once validated and expanded in these aforementioned ways, potential strengths of the "Companion for CAR-T" app include its ability to be personalized easily with information specific to individual CAR-T therapies, malignancies, and centers. Figure 1 Figure 1. Disclosures Banerjee: Sanofi: Consultancy; SparkCures: Consultancy; Pack Health: Research Funding. Sykes: Patient Discovery Solutions, Inc.: Current Employment. Shah: Amgen: Consultancy; Indapta Therapeutics: Consultancy; Sutro Biopharma: Research Funding; Sanofi: Consultancy; Teneobio: Research Funding; Precision Biosciences: Research Funding; Poseida: Research Funding; Karyopharm: Consultancy; Janssen: Research Funding; GSK: Consultancy; Kite: Consultancy; Nektar: Research Funding; Oncopeptides: Consultancy; CSL Behring: Consultancy; Bluebird Bio: Research Funding; BMS/Celgene: Research Funding; CareDx: Consultancy. Andreadis: Incyte: Honoraria; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; GenMAB: Research Funding; Merck: Research Funding; Novartis: Research Funding; Epizyme: Honoraria; Crispr Therapeutics: Research Funding; Atara: Consultancy, Honoraria; Karyopharm: Honoraria; TG Therapeutics: Honoraria; Kite: Honoraria; BMS/Celgene: Research Funding. Martin: Amgen: Research Funding; GlaxoSmithKline: Consultancy; Oncopeptides: Consultancy; Janssen: Research Funding; Sanofi: Research Funding. Shore: Patient Discovery Solutions, Inc.: Current Employment. Sodowick: Patient Discovery Solutions, Inc.: Current Employment. Wong: Amgen: Consultancy; Genentech: Research Funding; Fortis: Research Funding; Janssen: Research Funding; GloxoSmithKlein: Research Funding; Dren Biosciences: Consultancy; Caelum: Research Funding; BMS: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Herbal extract, rich with natural compounds, has been used for medicinal purpose such as treating neurological disorders such as cognitive defection for a long period of time, often without significant adverse effects. We compared AChE and BuChE – inhibition effect of total extracts and fractions of Huperzia serrata (Thunb.) Trevis. with alcaloid-rich extract. Our samples were subjected under supersonic extraction with ethanol 50o as solvent and fractionally extracted with n-hexane, EtOAc and n-butanol, respectively; alcaloid-rich extract was collected simutaneously. Ellman’s method was used to assay AChE and BuChE inhibition activity. Results: Alcaloid-rich extraction proved to be the superior AChE inhibiting agent, its activity nearly 6 fold of the most active Huperzia serrata extraction with IC50 value of 7.93 (5.43-10.98) µg/ml. While the fractions as well as the total extract did not provide any BuChE inhibition activity, alcaloid-rich extract showed weak ability (IC50 at 76.67 (64.78 – 91.84) µg/ml). Overall, the superior enzyme inhibition effect of alcaloid-rich extract might open a new approach in preventing and treating neurological disorders such as alzheimer’s. Keywords Huperzia serrata (Thunb.) Trevis, alcaloid, Acetylcholinesrerase inhibitors (AChE); butyrylcholinesterase (BuChE), Alzheimer. References [1] Dos Santos Picanco, Leide C et al., Alzheimer's disease: A review from the pathophysiology to diagnosis, new perspectives for pharmacological treatment, Current medicinal chemistry 25(26) (2018) 3141 - 3159. https://doi.org/10.2174/0929867323666161213101126.[2] B.M. McGleenon, K.B. Dynan, A.P. 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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus , is causing a serious worldwide COVID-19 pandemic. The emergence of strains with rapid spread and unpredictable changes is the cause of the increase in morbidity and mortality rates. A number of drugs as well as vaccines are currently being used to relieve symptoms, prevent and treat the disease caused by this virus. However, the number of approved drugs is still very limited due to their effectiveness and side effects. In such a situation, medicinal plants and bioactive compounds are considered a highly valuable source in the development of new antiviral drugs against SARS-CoV-2. This review summarizes medicinal plants and bioactive compounds that have been shown to act on molecular targets involved in the infection and replication of SARS-CoV-2. Keywords: Medicinal plants, bioactive compounds, antivirus, SARS-CoV-2, COVID-19 References [1] R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. 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This study aims to enhance the dissolution rate of a poorly-soluble drug, aspirin, by fabricating aspirin nanosuspensions using the anti-solvent precipitation. The study investigates the effect of the type of solvents, solvent to anti-solvent ratio, drug concentration, machines, stirring speed, ultrasonication technique and the temperature of solvent on the particle size and polydispersity index. The characterization of the original aspirin powder and nanoparticles was evaluated by differential scanning calorimetry and in vitro dissolution test. The results indicate that the selected formulation showed the smallest mean size of 228.2 ± 24.6 nm and a zeta potential of - 40.3 ± 2.5 mV. The differential scanning calorimetry analysis demonstrates that aspirin nanoparticles possessed lower crystallinity than the raw aspirin powder. The dissolution of nanoparticle was significantly higher compared with the original drug in the in vitro dissolution test. 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