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PURPOSE: Postoperative length of stay (LOS) after robot-assisted radical prostatectomy (RARP) is a potentially modifiable aspect of prostate cancer care. Our objective was to evaluate the use of same-day discharge (SDD) RARP and compare pre- and perioperative characteristics of these men with those who underwent hospitalization postoperatively. MATERIALS AND METHODS: Perioperative outcomes for patients undergoing RARP were evaluated from the Michigan Urological Surgery Improvement Collaborative (MUSIC) registry. Men were classified by hospital LOS: SDD, 1 day, and 2 days. Practice and surgeon-level variation of SDD and the change in SDD use over time were assessed. The primary outcome was 30-day readmission after RARP. RESULTS: We identified 10,249 men undergoing RARP in MUSIC from 2018 to 2022. Most patients had 1-day LOS (79.6%), with 2.8% undergoing SDD. The proportion of patients undergoing RARPs with SDD rose from 0.6% in 2018 to 1.2% in 2019 and 4.4% for 2020 to 2022. At least one SDD was performed in 12 of 28 MUSIC practices (42.9%) and by 52 of 138 urologists (37.7%). In multivariable analysis, odds of 30-day readmission were not significantly different between patients undergoing SDD and LOS 1 day (OR: 1.72, 95% CI: 0.92-3.22, P = .090). Limitations include retrospective, registry-based observational study with nonuniform utilization of SDD. CONCLUSIONS: Although more patients have undergone SDD after RARP beginning in 2018, rates across Michigan have remained < 5% annually. Importantly, patients undergoing SDD RARP did not experience significantly more readmissions compared to hospitalized patients. SDD appears safe and feasible for select patients who are motivated by this approach.
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BACKGROUND: Patients with lymph node positive (pN+) disease found at the time of radical prostatectomy with pelvic lymphadenectomy for clinically localized prostate cancer (CaP) are at high risk of disease persistence and progression. Contemporary management trends of pN+ CaP are not well described. MATERIALS AND METHODS: Patients in the Michigan Urologic Surgery Improvement Collaborative (MUSIC) with clinically localized prostate cancer who underwent radical prostatectomy between 2012 and 2023 with cN0/pN+ disease were identified. The primary outcome was to evaluate patient and practice-level factors associated with time to secondary post-RP treatment. Secondary outcomes included practice-level variation in management of pN+ CaP and rates of secondary treatment modality. To assess factors associated with secondary treatment, a Cox proportional hazards model of a 60-day landmark analysis was performed. RESULTS: We identified 666 patients with pN+ disease. Overall, 66% underwent secondary treatment within 12 months post-RP. About 19% of patients with detectable post-RP PSA did not receive treatment. Of patients receiving secondary treatment after 60-days post-RP, 34% received androgen deprivation therapy (ADT) alone, 27% received radiation (RT) alone, 36% received combination, and 4% received other systemic therapies. In the multivariable model, pathologic grade group (GG)3 (HR 1.5; 95%CI: 1.05-2.14), GG4-5 (HR 1.65; 95%CI: 1.16-2.34), positive margins (HR 1.46; 95%CI: 1.13-1.88), and detectable postoperative PSA ≥0.1 ng/ml (HR 3.46; 95%CI: 2.61-4.59) were significantly associated with secondary post-RP treatment. There was wide variation in adjusted practice-level 12-month secondary treatment utilization (28%-79%). CONCLUSIONS: The majority pN+ patients receive treatment within 12 months post-RP which was associated with high-risk pathological features and post-RP PSA. Variation in management of pN+ disease highlights the uncertainty regarding the optimal management. Understanding which patients will benefit from secondary treatment, and which type, will be critical to minimize variation in care.
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Prostatectomia , Neoplasias da Próstata , Melhoria de Qualidade , Humanos , Masculino , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Prostatectomia/métodos , Pessoa de Meia-Idade , Idoso , Excisão de Linfonodo , Metástase Linfática , Estudos Retrospectivos , Linfonodos/patologia , MichiganRESUMO
After radical prostatectomy, adjuvant therapy should be used sparingly when prostate-specific antigen (PSA) is undetectable. Instead, early salvage therapy is recommended for PSA recurrence. Patients with PSA persistence after prostatectomy are at high risk and should be offered consolidative therapy.
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OBJECTIVE: To determine the incidence of incidental prostate cancer detection (iPCa) after holmium laser enucleation of the prostate (HoLEP). The published rate of iPCa after HoLEP is widely variable from 7% to 23% and we aim to define preoperative risk factors for iPCa to inform risk-adjusted preoperative evaluation for PCa. METHODS: Consecutive patients undergoing HoLEP from 2018 to 2022 were included and comprehensive clinical data abstracted from a prospectively maintained database. iPCa was defined as a diagnosis of PCa on pathologic examination of the HoLEP specimen. Patients with and without iPCa were compared with respect to preoperative clinical variables. RESULTS: Of 913 HoLEP patients, 183 (20%) were diagnosed with iPCa. Most patients (95%) had a preoperative prostate-specific antigen (PSA), 9% had negative MRI, and 30% had negative prostate biopsy. On multivariable analysis, PSA density (OR 1.06; 95% CI 1.03, 1.10; P < .001), preoperative biopsy status (OR 0.47, CI 0.30, 0.75; P = .002), and current 5-alpha reductase inhibitor use (OR 0.64, CI 0.43, 0.97; P = .034), were associated with iPCa diagnosis. CONCLUSION: In a significantly prescreened population, we identified a 20% rate of iPCa after HoLEP. Preoperative characteristics associated with iPCa diagnosis included increasing age, increasing PSA density, and current 5-alpha reductase inhibitor use. However, these factors alone may be of limited clinical utility to prospectively identify patients at high risk of iPCa diagnosis. We suggest and advocate for development of a standardized, risk-adapted evaluation focused on expanded use of imaging and selective biopsy to prioritize identification of clinically significant PCa prior to nononcologic surgery.
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Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Neoplasias da Próstata , Masculino , Humanos , Próstata/cirurgia , Próstata/patologia , Antígeno Prostático Específico , Hiperplasia Prostática/diagnóstico , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/complicações , Lasers de Estado Sólido/uso terapêutico , Inibidores de 5-alfa Redutase , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Hólmio , Resultado do TratamentoRESUMO
Excessive opioid prescribing following surgery creates a reservoir of unused medications available for diversion and abuse. We conducted a cohort study examining the impact of clinic-based, surgeon-initiated strategies using an activated charcoal bag (ACB) system on disposal of unused opioids. Among patients undergoing a variety of general surgery procedures, 67% of those with unused opioids disposed of them using the ACB. Our findings demonstrate practical ways to incorporate opioid disposal into surgical practice as a complement to judicious opioid prescribing.
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OBJECTIVE: To explore the effect of Agent Orange (AO) exposure on bladder cancer (BCa) outcomes in patients receiving Bacillus Calmette-Guérin (BCG) for non-muscle invasive BCa (NMIBC). METHODS: We retrospectively examined the association between AO exposure in patients with NMIBC in national veterans affairs databases who were being treated with BCG. Patients were diagnosed with NMIBC from 2000 to 2010 with follow-up through 2018. Clinical, pathological, and demographic variables were compared by AO exposure. Associations of AO exposure with recurrence, progression, and cancer-specific survival were performed using Cox proportional hazard models after inverse propensity score weighting and competing risks adjustments. We also assessed the association of AO exposure on grade and stage via multivariable logistic regression models. RESULTS: A total of 7651 patients were identified of which 753 (9.8%) were exposed to AO. The median follow-up time was 130 months. The AO-exposed patients were younger (age 61 vs 71 years, P <.001), but had similar Charlson comorbidity scores and stage/grade distribution as the non-AO exposed patients. AO exposure was not associated with higher grade or stage. In our Cox multivariable analyses, AO exposure was not associated with worse recurrence (hazard ratio (HR) 0.89, 95% confidence interval (CI) 0.72-1.10, P = .29), progression (HR 1.08, 95% CI 0.86-1.36, P = .51), or cancer-specific survival (HR 1.31, 95% CI 0.92-1.87, P = .13). CONCLUSION: AO exposure was not associated with worse oncologic outcomes in patients receiving BCG for NMIBC. While this is reassuring, additional research is needed in other patient populations and disease states to determine if the effect is consistent.
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Agente Laranja , Neoplasias não Músculo Invasivas da Bexiga , Neoplasias da Bexiga Urinária , Humanos , Pessoa de Meia-Idade , Adjuvantes Imunológicos/uso terapêutico , Administração Intravesical , Agente Laranja/uso terapêutico , Vacina BCG/efeitos adversos , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias não Músculo Invasivas da Bexiga/complicações , Neoplasias não Músculo Invasivas da Bexiga/terapia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/terapia , IdosoRESUMO
Abiotic stresses, including salinity stress, affect numerous crops, causing yield reduction, and, as a result, important economic losses. Extracts from the brown alga Ascophyllum nodosum (ANE), and compounds secreted by the Pseudomonas protegens strain, CHA0, can mitigate these effects by inducing tolerance against salt stress. However, the influence of ANE on P. protegens CHA0 secretion, and the combined effects of these two biostimulants on plant growth, are not known. Fucoidan, alginate, and mannitol are abundant components of brown algae and of ANE. Reported here are the effects of a commercial formulation of ANE, fucoidan, alginate, and mannitol, on pea (Pisum sativum), and on the plant growth-promoting activity of P. protegens CHA0. In most situations, ANE and fucoidan increased indole-3-acetic acid (IAA) and siderophore production, phosphate solubilization, and hydrogen cyanide (HCN) production by P. protegens CHA0. Colonization of pea roots by P. protegens CHA0 was found to be increased mostly by ANE and fucoidan in normal conditions and under salt stress. Applications of P. protegens CHA0 combined with ANE, or with fucoidan, alginate, and mannitol, generally augmented root and shoot growth in normal and salinity stress conditions. Real-time quantitative PCR analyses of P. protegens revealed that, in many instances, ANE and fucoidan enhanced the expression of several genes involved in chemotaxis (cheW and WspR), pyoverdine production (pvdS), and HCN production (hcnA), but gene expression patterns overlapped only occasionally those of growth-promoting parameters. Overall, the increased colonization and the enhanced activities of P. protegens CHA0 in the presence of ANE and its components mitigated salinity stress in pea. Among treatments, ANE and fucoidan were found responsible for most of the increased activities of P. protegens CHA0 and the improved plant growth.
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Objective: To explore patient and treatment factors explaining the association between spine injury and opioid misuse. Design: Prospective cohort study. Setting: Level I trauma center in a Midwestern city. Participants: English speaking patients aged 18 to 75 on Trauma and Orthopedic Surgical Services receiving opioids during hospitalization and prescribed at discharge. Exposure: Spine injury on the Abbreviated Injury Scale. Main outcome measures: Opioid misuse was defined by using opioids: in a larger dose, more often, or longer than prescribed; via a non-prescribed route; from someone other than a prescriber; and/or use of heroin or opium. Exploratory factor groups included demographic, psychiatric, pain, and treatment factors. Multivariable logistic regression estimated the association between spine injury and opioid misuse when adjusting for each factor group. Results: Two hundred eighty-five eligible participants consented of which 258 had baseline injury location data and 224 had follow up opioid misuse data. Most participants were male (67.8%), white (85.3%) and on average 43.1âyears old. One-quarter had a spine injury (25.2%). Of those completing follow-up measures, 14 (6.3%) developed misuse. Treatment factors (injury severity, intubation, and hospital length of stay) were significantly associated with spine injury. Spine injury significantly predicted opioid misuse [odds ratio [OR] 3.20, 95% confidence interval [CI] (1.05, 9.78)]. In multivariable models, adjusting for treatment factors attenuated the association between spine injury and opioid misuse, primarily explained by length of stay. Conclusion: Spine injury exhibits a complex association with opioid misuse that predominantly operates through treatment factors. Spine injury patients may represent a subpopulation requiring early intervention to prevent opioid misuse.
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OBJECTIVE: To examine our outpatient urologic surgery cohort for trends in opioid consumption, given the lack of consensus on opioid prescription after outpatient urologic procedures. While opioids have a role in multimodal postoperative analgesia, there is emerging data that they may not be routinely required after pediatric surgery. METHODS: Data on opioid use was prospectively collected over 16 months via postoperative telephone calls to caregivers of patients undergoing outpatient urologic surgery. Patient characteristics, surgery type, analgesia, and opioid prescription and usage information were recorded. Patients were prescribed as needed oxycodone and scheduled acetaminophen and ibuprofen for 48 hours, then as needed. The relationships between the log mean of the number of opioid doses used and age, type of surgery, race, and opioid prescription were modelled using negative binomial regression with the robust standard errors. RESULTS: Two hundred sixty-five patients were included. They were predominantly male with median age 2.6 years. The mean number of opioid doses prescribed per patient was 5.8 (SD 2.8, range 3-20). Over half of patients used no opioids, and mean opioid use was one dose. Those prescribed >5 doses took on average 3.4 times more doses compared to those prescribed >5 (P = .0003), and this was the only factor significantly associated with the amount of opioid used. CONCLUSION: Our findings suggest that opioids are over-prescribed after outpatient pediatric urologic surgery, with 95% of patients having leftover medication and 54% not using any opioids at all. While opioid requirements were low across all sub-cohorts, patients who were prescribed more opioid doses used significantly more doses.
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Transtornos Relacionados ao Uso de Opioides , Oxicodona , Humanos , Criança , Masculino , Pré-Escolar , Feminino , Oxicodona/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Ibuprofeno/uso terapêutico , Acetaminofen/uso terapêutico , Pacientes Ambulatoriais , Analgésicos Opioides/uso terapêutico , Padrões de Prática MédicaRESUMO
BACKGROUND: Despite compelling links between excess body weight and cancer, body mass index (BMI) cut-points, or thresholds above which cancer incidence increased, have not been identified. The objective of this study was to determine if BMI cut-points exist for 14 obesity-related cancers. SUBJECTS/METHODS: In this retrospective cohort study, patients 18-75 years old were included if they had ≥2 clinical encounters with BMI measurements in the electronic health record (EHR) at a single academic medical center from 2008 to 2018. Patients who were pregnant, had a history of cancer, or had undergone bariatric surgery were excluded. Adjusted logistic regression was performed to identify cancers that were associated with increasing BMI. For those cancers, BMI cut-points were calculated using adjusted quantile regression for cancer incidence at 80% sensitivity. Logistic and quantile regression models were adjusted for age, sex, race/ethnicity, and smoking status. RESULTS: A total of 7079 cancer patients (mean age 58.5 years, mean BMI 30.5 kg/m2) and 270,441 non-cancer patients (mean age 43.8 years, mean BMI 28.8 kg/m2) were included in the study. In adjusted logistic regression analyses, statistically significant associations were identified between increasing BMI and the incidence of kidney, thyroid, and uterine cancer. BMI cut-points were identified for kidney (26.3 kg/m2) and uterine (26.9 kg/m2) cancer. CONCLUSIONS: BMI cut-points that accurately predicted development kidney and uterine cancer occurred in the overweight category. Analysis of multi-institutional EHR data may help determine if these relationships are generalizable to other health care settings. If they are, incorporation of BMI into the screening algorithms for these cancers may be warranted.
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Obesidade , Neoplasias Uterinas , Adolescente , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/epidemiologia , Sobrepeso/diagnóstico , Estudos Retrospectivos , Adulto JovemRESUMO
Atypical porcine pestivirus (APPV), an RNA virus member of the Flaviviridae family, has been associated with congenital tremor in newborn piglets. Previously reported quantitative polymerase chain reaction (qPCR)-based assays were unable to detect APPV in novel cases of congenital tremor originated from multiple farms from U.S. Midwest (MW). These assays targeted the viral polyprotein coding genes, which were shown to display substantial variation, with sequence identity ranging from 58.2% to 70.7% among 15 global APPV strains. In contrast, the 5'-untranslated region (5' UTR) was found to have a much higher degree of sequence conservation. In order to obtain the complete 5' UTR of the APPV strains originated from MW, the 5' end of the viral cDNA was obtained by using template switching approach followed by amplification and dideoxy sequencing. Eighty one percent of the 5' UTR was identical across 14 global and 5 MW strains with complete or relatively complete 5' UTR. Notably, some of the most highly conserved 5' UTR segments overlapped with potentially important regions of an internal ribosome entry site (IRES), suggesting their functional role in viral protein translation. A newly designed single qPCR assay, targeting 100% conserved 5' UTR regions across 19 strains, was able to detect APPV in samples of well documented cases of congenital tremor which originated from five MW farm sites (1-18 samples/site). As these fully conserved 5' UTR sequences may have functional importance, we expect that assays targeting this region would broadly detect APPV strains that are diverse in space and time.
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Infecções por Pestivirus , Pestivirus , Doenças dos Suínos , Animais , Variação Genética , Pestivirus/genética , Infecções por Pestivirus/epidemiologia , Infecções por Pestivirus/veterinária , Filogenia , Suínos , Doenças dos Suínos/diagnóstico , Doenças dos Suínos/epidemiologiaRESUMO
Management options for small renal masses include active surveillance, partial nephrectomy, radical nephrectomy, and thermal ablation. For tumors typically ≤3 cm in size, thermal ablation is a good option for those desiring an alternative to surgery or active surveillance, especially in patients who are considered high surgical risk. We favor microwave ablation because of the more rapid heating, higher temperatures that overcome the heat sink effect of vessels, reproducible cell kill, and a highly visible ablation zone formed by water vapor that corresponds well to the zone of necrosis. For central tumors, we favor cryoablation because of the slower formation of the ablation zone and less likelihood of damage to the collecting system. With microwaves, it is important to monitor the ablation zone in real time (ultrasound is the best modality for this purpose), avoid direct punctures of the collecting system, and to place probes tangential to the collecting system to avoid burning open a persistent tract between the urothelium and extrarenal spaces or causing strictures. The surgical steps described in this video cover our use of high-frequency jet ventilation with general anesthesia to minimize organ motion, initial imaging and targeting, probe insertion, hydrodissection (a technique that enables displacement of adjacent structures), the ablation itself, and finally our dressing. Postoperative cares typically consist of observation with a same-day discharge or an overnight stay. Follow-up includes a magnetic resonance imaging abdomen with and without contrast, chest X-ray, and laboratories (basic metabolic panel, complete blood count, and C-reactive protein) 6 months postablation. Overall, percutaneous microwave ablation is an effective and safe treatment option for renal cell carcinoma in both T1a and T1b tumors in selected patients with multiple studies showing excellent oncologic outcomes when compared with partial and radical nephrectomy.
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Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Micro-Ondas/uso terapêutico , Nefrectomia , Resultado do TratamentoRESUMO
OBJECTIVE: To improve prostate cancer screening for high-risk men, we developed an early detection clinic for patients at high genetic risk of developing prostate cancer. Despite the rapidly growing understanding of germline variants in driving aggressive prostate cancer and the increased availability of genetic testing, there is little evidence surrounding how best to screen these men. METHODS: We are reporting on the first 45 patients enrolled, men between the ages of 35-75, primarily with known pathogenic germline variants in prostate cancer susceptibility genes. Screening consists of an intake lifestyle survey, PSA, DRE, and SelectMDx urine assay. A biopsy was recommended for any of the following indications: 1) abnormal DRE, 2) PSA above threshold, or 3) SelectMDx above threshold. The primary outcomes were number needed to screen, and number needed to biopsy to diagnose a patient with prostate cancer. RESULTS: Patients enrolled in the clinic included those with BRCA1 (n=7), BRCA2 (n=16), Lynch Syndrome (n=6), and CHEK2 (nâ¯=â¯4) known pathogenic germline variants. The median age and PSA were 58 (range 35-71) and 1.4 ng/ml (range 0.1-11.4 ng/ml), respectively. 12 patients underwent a prostate needle biopsy and there were 4positive biopsies for prostate cancer. CONCLUSION: These early data support the feasibility of opening a dedicated clinic for men at high genetic risk of prostate cancer. This early report on the initial enrollment of our long-term study will help optimize early detection protocols and provide evidence for personalized prostate cancer screening in men with key pathogenic germline variants.
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Detecção Precoce de Câncer , Predisposição Genética para Doença , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Adulto , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Biópsia , Quinase do Ponto de Checagem 2/genética , Neoplasias Colorretais Hereditárias sem Polipose/genética , Exame Retal Digital , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Estilo de Vida , Masculino , Anamnese , Pessoa de Meia-Idade , Inquéritos Nutricionais , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Fatores de Risco , UrináliseRESUMO
Brown alga Ectocarpus sp. belongs to Phaeophyceae, a class of macroalgae that evolved complex multicellularity. Ectocarpus sp. is a dominant seaweed in temperate regions, abundant mostly in the intertidal zones, an environment with high levels of abiotic stresses. Previous transcriptomic analysis of Ectocarpus sp. revealed several genes consistently induced by various abiotic stresses; one of these genes is Esi0017_0056, which encodes a protein with unknown function. Bioinformatics analyses indicated that the protein encoded by Esi0017_0056 is soluble and monomeric. The protein was successfully expressed in Escherichia coli,Arabidopsis thaliana and Nicotiana benthamiana. In A. thaliana the gene was expressed under constitutive and stress inducible promoters which led to improved tolerance to high salinity and temperature stresses. The expression of several key abiotic stress-related genes was studied in transgenic and wild type A. thaliana by qPCR. Expression analysis revealed that genes involved in ABA-induced abiotic stress tolerance, K+ homeostasis, and chaperon activities were significantly up-regulated in the transgenic line. This study is the first report in which an unknown function Ectocarpus sp. gene, highly responsive to abiotic stresses, was successfully expressed in A. thaliana, leading to improved tolerance to salt and temperature stress.
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Adaptação Fisiológica , Proteínas de Algas/metabolismo , Arabidopsis/genética , Arabidopsis/fisiologia , Temperatura Alta , Phaeophyceae/metabolismo , Salinidade , Estresse Fisiológico , Adaptação Fisiológica/genética , Proteínas de Algas/química , Proteínas de Algas/genética , Arabidopsis/crescimento & desenvolvimento , Eletrólitos/metabolismo , Escherichia coli/metabolismo , Regulação da Expressão Gênica de Plantas , Filogenia , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas/genética , Plântula/genética , Estresse Fisiológico/genética , Nicotiana/metabolismoRESUMO
OBJECTIVE: To interrogate the National Veterans Health Administration (VA) database to determine if beta-blocker use at time of initiation of androgen therapy deprivation (ADT) would result in improved oncological outcomes in advanced prostate cancer (PCa). METHODS: All men diagnosed with high risk PCa (PSA >20) from 2000-2008 who were on ADT ≥ 6 months were identified. Patients receiving ADT concurrently with primary radiation therapy were excluded. Pharmacy data was interrogated for all beta-blockers, but then focused on the selective beta-1 blocker metoprolol. Cox proportional hazards ratios were calculated for overall survival (OS), PCa specific survival (CSS) and skeletal related events (SREs). RESULTS: In 39,198 patients with high risk PCa on ADT, use of any beta-blocker was not associated with improvement in OS, CSS, or SREs. Further analyses focusing on metoprolol found that 10,224 (31.9%) had used metoprolol while 21,834 had no beta-blocker use. Multivariable analysis with Inverse Propensity Score Weighting, adjusted for factors including PSA, Gleason score, and duration ADT, found that utilization of metoprolol was not associated with improvement in OS (hazard ratio [HR] 0.97, P = .19), CSS (HR 0.94, P = .23) or SREs (HR 0.98, P = .79). CONCLUSION: In this large cohort, metoprolol use in conjunction with ADT in high risk PCa was not associated with improvement in OS, CSS, or risk of SRE. In contrast to a recent smaller clinical study, our data strongly suggests no cancer specific benefit to beta-blocker use in advanced PCa.
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Antagonistas de Receptores Adrenérgicos beta 1/uso terapêutico , Antagonistas de Androgênios/uso terapêutico , Neoplasias Ósseas/secundário , Metoprolol/uso terapêutico , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Humanos , Masculino , Modelos de Riscos Proporcionais , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologia , United States Department of Veterans AffairsRESUMO
Sustainable agricultural practices increasingly demand novel, environmentally friendly compounds which induce plant immunity against pathogens. Stimulating plant immunity using seaweed extracts is a highly viable strategy, as these formulations contain many bio-elicitors (phyco-elicitors) which can significantly boost natural plant immunity. Certain bioactive elicitors present in a multitude of extracts of seaweeds (both commercially available and bench-scale laboratory formulations) activate pathogen-associated molecular patterns (PAMPs) due to their structural similarity (i.e., analogous structure) with pathogen-derived molecules. This is achieved via the priming and/or elicitation of the defense responses of the induced systemic resistance (ISR) and systemic acquired resistance (SAR) pathways. Knowledge accumulated over the past few decades is reviewed here, aiming to explain why certain seaweed-derived bioactives have such tremendous potential to elicit plant defense responses with considerable economic significance, particularly with increasing biotic stress impacts due to climate change and the concomitant move to sustainable agriculture and away from synthetic chemistry and environmental damage. Various extracts of seaweeds display remarkably different modes of action(s) which can manipulate the plant defense responses when applied. This review focuses on both the similarities and differences amongst the modes of actions of several different seaweed extracts, as well as their individual components. Novel biotechnological approaches for the development of new commercial products for crop protection, in a sustainable manner, are also suggested.
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Produtos Biológicos/farmacologia , Imunidade Inata/efeitos dos fármacos , Doenças das Plantas/prevenção & controle , Imunidade Vegetal/efeitos dos fármacos , Alga Marinha , Animais , Produtos Biológicos/isolamento & purificação , Produtos Biológicos/uso terapêutico , Humanos , Imunidade Inata/fisiologia , Doenças das Plantas/imunologia , Imunidade Vegetal/fisiologia , Alga Marinha/isolamento & purificaçãoRESUMO
Food availability represents a major worldwide concern due to population growth, increased demand, and climate change. Therefore, it is imperative to identify compounds that can improve crop performance. Plant biostimulants have gained prominence because of their potentials to increase germination, productivity and quality of a wide range of horticultural and agronomic crops. Phosphite (Phi), an analog of orthophosphate, is an emerging biostimulant used in horticulture and agronomy. The aim of this study was to uncover the molecular mechanisms through which Phi acts as a biostimulant with potential effects of overall plant growth. Field and greenhouse experiments, using 4 potato cultivars, showed that following Phi applications, plant performance, including several physio-biochemical traits, crop productivity, and quality traits, were significantly improved. RNA sequencing of control and Phi-treated plants of cultivar Xingjia No. 2, at 0 h, 6 h, 24 h, 48 h, 72 h and 96 h after the Phi application for 24 h revealed extensive changes in the gene expression profiles. A total of 2856 differentially expressed genes were identified, suggesting that multiple pathways of primary and secondary metabolism, such as flavonoids biosynthesis, starch and sucrose metabolism, and phenylpropanoid biosynthesis, were strongly influenced by foliar applications of Phi. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses associated with defense responses revealed significant effects of Phi on a plethora of defense mechanisms. These results suggest that Phi acted as a biostimulant by priming the plants, that was, by triggering dynamic changes in gene expression and modulating metabolic fluxes in a way that allowed plants to perform better. Therefore, Phi usage has the potential to improve crop yield and health, alleviating the challenges posed by the need of feeding a growing world population, while minimizing the agricultural impact on human health and environment.
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Fosfitos/farmacologia , Solanum tuberosum/efeitos dos fármacos , Metabolismo dos Carboidratos/efeitos dos fármacos , Solanum tuberosum/crescimento & desenvolvimento , Solanum tuberosum/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Transcriptoma/efeitos dos fármacosRESUMO
Mannitol is abundant in a wide range of organisms, playing important roles in biotic and abiotic stress responses. Nonetheless, mannitol is not produced by a vast majority of plants, including many important crop plants. Mannitol-producing transgenic plants displayed improved tolerance to salt stresses though mannitol production was rather low, in the µM range, compared to mM range found in plants that innately produce mannitol. Little is known about the molecular mechanisms underlying salt tolerance triggered by low concentrations of mannitol. Reported here is the production of mannitol in Arabidopsis thaliana, by expressing two mannitol biosynthesis genes from the brown alga Ectocarpus sp. strain Ec32. To date, no brown algal genes have been successfully expressed in land plants. Expression of mannitol-1-phosphate dehydrogenase and mannitol-1-phosphatase genes was associated with the production of 42.3-52.7 nmol g-1 fresh weight of mannitol, which was sufficient to impart salinity and temperature stress tolerance. Transcriptomics revealed significant differences in the expression of numerous genes, in standard and salinity stress conditions, including genes involved in K+ homeostasis, ROS signaling, plant development, photosynthesis, ABA signaling and secondary metabolism. These results suggest that the improved tolerance to salinity stress observed in transgenic plants producing mannitol in µM range is achieved by the activation of a significant number of genes, many of which are involved in priming and modulating the expression of genes involved in a variety of functions including hormone signaling, osmotic and oxidative stress, and ion homeostasis.