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Purpose: The purpose of this study was to investigate the microleakage of atraumatic glass ionomer restorations with and without silver diammine fluoride (SDF) application. Restorations with SDF are termed silver-modified atraumatic restorations (SMART). Methods: Sixty carious extracted permanent teeth were randomly allocated to two SMART groups and two control groups (n equals 15 per group) for a total of four groups. After selective caries removal, test specimens were treated with 38 percent SDF and polyacrylic acid conditioner was applied and rinsed; teeth were restored with Fuji IX GP® glass ionomer (n equals 15) or with SMART Advantage™ glass ionomer (SAGI; n equals 15). For control groups, specimens were restored with their respective GI material after selective caries removal, both without SDF. Restored teeth were placed in Dulbecco's Phosphate-Buffered Saline solution at 37 degrees Celsius for 24 hours. Teeth were thermocycled between five and 55 degrees Celsius for 1,000 cycles, stained with two percent basic fuchsin, sectioned, and visually inspected for microleakage utilizing stereomicroscopy on a four-point scale. Data were statistically analyzed using Kruskal-Wallis one-way analysis of variance on ranks using Dunn's method (P<0.05). Results: Microleakage between the two SMART restoration groups was insignificant. SAGI alone demonstrated significantly more microleakage than all other groups. There was no statistical significance between the Fuji IX GP® control group and the two SMART restoration groups. Conclusions: This in vitro study indicated that silver diammine fluoride placed before glass ionomer restoration does not increase microleakage. Polyacrylic acid may be used after SDF placement without increasing microleakage.
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Tratamento Dentário Restaurador sem Trauma , Cárie Dentária , Infiltração Dentária , Fluoretos Tópicos , Cimentos de Ionômeros de Vidro , Compostos de Prata , Infiltração Dentária/prevenção & controle , Humanos , Compostos de Prata/química , Cimentos de Ionômeros de Vidro/química , Tratamento Dentário Restaurador sem Trauma/métodos , Fluoretos Tópicos/química , Cárie Dentária/prevenção & controle , Cariostáticos/química , Compostos de Amônio Quaternário/química , Viscosidade , Resinas Acrílicas/química , Restauração Dentária Permanente/métodosRESUMO
Functions of vitellogenins have been in the limelight of fish reproductive physiology research for decades. The Vtg system of acanthomorph teleosts consists of two complete forms of Vtgs (VtgAa and VtgAb) and an incomplete form, VtgC. Insufficient uptake and processing of Vtgs and their yolk proteins lead to inadequate oocyte hydration ensuing failure in acquisition of egg buoyancy and early developmental deficiencies. This review presents a summary of our studies on utilization of multiple Vtgs in species with different egg buoyancy characteristics, as examples. Studies of moronids revealed limited degradation of all three forms of lipovitellin heavy chain derived from their three respective forms of Vtg, by which they contribute to the free amino acid pool driving oocyte hydration during oocyte maturation. In later studies, CRISPR/Cas9 was employed to invalidate zebrafish type I, type II and type III Vtgs, which are orthologs of acanthamorph VtgAa, VtgAb and VtgC, respectively. Results revealed type I Vtg to have essential developmental and nutritional functions in both late embryos and larvae. Genomic disturbance of type II Vtg led to high mortalities during the first 24 h of embryonic development. Despite being a minor form of Vtg in zebrafish and most other species, type III Vtg was also found to contribute essentially to the developmental potential of zebrafish zygotes and early embryos. Apart from severe effects on progeny survival, these studies also disclosed previously unreported regulatory effects of Vtgs on fecundity and fertility, and on embryo hatching. We recently utilized parallel reactions monitoring based liquid chromatography tandem mass spectrometry to assess the processing and utilization of lipovitellins derived from different forms of Vtg in Atlantic halibut and European plaice. Results showed the Lv heavy chain of VtgAa (LvHAa) to be consumed during oocyte maturation and the Lv light chain of VtgAb (LvLAb) to be utilized specifically during late larval stages, while all remaining YPs (LvLAa, LvHAb, LvHC, and LvLC) were utilized during or after hatching up until first feeding in halibut. In plaice, all YPs except LvHAa, which similarly to halibut supports oocyte maturation, are utilized from late embryo to late larval development up until first feeding. The collective findings from these studies affirm substantial disparity in modes of utilization of different types of Vtgs among fish species with various egg buoyancy characteristics, and they reveal previously unknown regulatory functions of Vtgs in maintenance of reproductive assets such as maternal fecundity and fertility, and in embryonic hatching. Despite the progress that has been made over the past two decades by examining multiple Vtgs and their functions, a higher complexity of these systems with much greater diversity between species in modes of Vtg utilization is now evident. Further research is needed to reveal novel ways each species has evolved to utilize these complex multiple Vtg systems and to discover unifying principles for this evolution in fishes of diverse lineages, habitats and life history characteristics.
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Perciformes , Vitelogeninas , Animais , Vitelogeninas/metabolismo , Peixe-Zebra/metabolismo , Peixes/metabolismo , Oócitos/metabolismo , Oogênese/genética , Perciformes/metabolismoRESUMO
OBJECTIVE: To explore the data comparing single- vs multi-use catheters for clean intermittent catheterisation (CIC), consider if the widespread use of single-use catheters is warranted given the cost and environmental impact, and put forth ideas for future consideration. METHODS: A primary literature review was performed in PubMed over the past 50 years. Studies that performed comparative analysis of single- and multi-use catheters were included in our review. All studies that reported on primary data were narratively summarised. RESULTS: A total of 11 studies were identified that reported on primary data comparing single- and multi-use catheters. There was no appreciable evidence suggesting reusable multi-use catheters were inferior to single-use catheters from an infection or usability standpoint. In addition, the environmental and monetary burden of single-use catheters is significant. CONCLUSIONS: The intermittent catheter landscape in the USA has a complex past: defined by policy, shaped by industry, yet characterised by a paucity of data demonstrating superiority of single-use over multi-use catheters. We believe that the aversion to reusable catheters by many patients and healthcare professionals is unwarranted, especially given the cost and environmental impact. Moving forward, better comparative data and more sustainable practices are needed.
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Reutilização de Equipamento , Humanos , Reutilização de Equipamento/economia , Equipamentos Descartáveis/economia , Meio Ambiente , Cateteres Urinários , Cateterismo Uretral Intermitente/instrumentaçãoRESUMO
PURPOSE: The treated natural history of nonmetastatic plasmacytoid variant of bladder cancer (PV-BCa) is poorly understood owing to its rarity. We sought to examine the disease recurrence and metastasis patterns in this select group of patients in order to identify opportunities for intervention. MATERIALS AND METHODS: We conducted a natural language processing algorithm-augmented retrospective chart review of 56 consecutive patients who were treated with curative intent for nonmetastatic PV-BCa at our institution between 1998 and 2018. Kaplan-Meier and multivariable Cox regression methods were used for survival analyses. RESULTS: The stage at presentation was: ≤ cT2N0 in 22 (39.3%), cT3N0 in 15 (26.8%), cT4N0 in 13 (23.2%), and ≥ cN1 in 6 patients (10.7%). Forty-nine patients (87.5%) received chemotherapy, and 42 (75%) were able to undergo the planned surgery. Notably, only 4 patients (7.2%) had pT0 stage, while 22 (52.4%) had pN+ disease at the time of surgery. At 36-month follow-up, 28.4% of patients (95% CI: 22.1%-34.5%) were alive and 22.2% (95% CI: 16.1%-28.5%) were free of metastatic disease. The benefit of surgical extirpation was stage specific: successful completion of surgery was associated with improved metastasis-free survival (at 36 months 32.4% vs 0%, log-rank P < .001) in patients with localized or locally advanced disease (≤cT2N0/cT3N0); however, in patients with regionally advanced disease (cT4N0/≥cN1), consolidative surgery following chemotherapy was not associated with improved metastasis-free survival (12.5% vs 10% at 36 months, log-rank P = .49). The median time to metastasis from primary treatment end was 6.5 months (IQR: 2.9-14.7). The predominant site of recurrence/metastasis was the peritoneum (76.1%), either in isolation or along with extraperitoneal lesions. Salvage immunotherapy in these patients significantly reduced the risk of death (HR = 0.11, P = .001). CONCLUSIONS: PV-BCa is a disease with high lethality. Despite multimodal treatment, a vast majority of patients develop atypical intraperitoneal metastasis soon after therapy and rapidly succumb to it. Clinical trials evaluating utility of hyperthermic intraperitoneal chemotherapy and/or immunotherapy may be warranted in this high-risk population.
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Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Terapia Combinada , Resultado do TratamentoRESUMO
INTRODUCTION: Long-term urodynamic (UDS) and urethral pressure profilometry (UPP) parameters in women with voiding phase dysfunction following an anti-incontinence (AI) procedure have been poorly characterized. We report our 10-year UDS findings in women with voiding phase dysfunction after AI procedure, who underwent urethrolysis. METHODS: We identified sequential records containing urethrolysis current procedural terminology codes over a 10-year period. Records of women with preoperative UDS were reviewed for demographics, UDS tracing, and outcomes following urethrolysis. RESULTS: Twenty-five women (mean age 60 years) had voiding phase dysfunction and underwent urethrolysis at a mean of 47 months (interquartile range [IQR] 12-61) after AI procedure. Preoperatively, six (24%) women required intermittent catheterization. Free uroflowmetry revealed a mean maximum peak flow (Qmax) of 9.6 ml/s (IQR 7.0-11.0), voided volume of 137 ml (IQR 81-169), and postvoid residual of 167 ml (IQR 43-288). UDS revealed a mean UPP length of 24 mm (IQR 20-27), UPP closure pressure of 78 cmH2O (IQR 59-103), detrusor pressure at maximum flow (Pdet@Qmax) of 31 cmH2O (IQR 19-43), Qmax of 7.9 ml/s (IQR 5.0-12.0), bladder outlet obstruction index of 15 (IQR 0-34), and bladder contractility index of 71 (IQR 60-81). UPP length was significantly associated (Pearson correlation, p<0.05) with bladder outlet obstruction index (r=0.80), Pdet@Qmax (r=0.75), and time since AI procedure (r=-0.70). UPP closure pressure was significantly associated with age (r=-0.64), volume of first (r=-0.64) and strong (r=-0.78) desire, and capacity (r=-0.71). Following urethrolysis, spontaneous voiding was achieved in 23 (92%) women at followup (mean 308 days). CONCLUSIONS: UPP may help characterize outlet parameters in women with voiding phase dysfunction following an AI procedure, who ultimately undergo urethrolysis.
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OBJECTIVE: To compare outcomes of Aquablation in men with acute and chronic urinary retention. METHODS: We conducted a retrospective review of all men undergoing Aquablation resection of the prostate between May 2021 and August 2022. Men were classified as having acute urinary retention if they required either intermittent or indwelling catheter and chronic urinary retention if they had a postvoid residual >300 mL prior to surgery. We compared success rates and time to passage of trial without catheter as well as complication rates to those with no retention. RESULTS: A total of 113 men underwent Aquablation including 28 with acute retention and 16 with chronic retention. Failure of initial void trial was significantly higher in patients with preoperative urinary retention (40%) and chronic retention with postvoid residual >300 mL (12.5%) compared to those with no retention (7.2%, P < .001). Among men with acute and chronic retention 98% were voiding spontaneously at a mean 5months follow-up. There was no difference in utilization of postoperative prostate medications, complications, International Prostate Symptom Score or uroflowmetry among men with acute, chronic, or no retention. CONCLUSION: Aquablation is an effective method for treatment of men with urinary retention, with 98% achieving spontaneous voiding regardless of preoperative urodynamic findings. Men in acute retention prior to surgery were more likely to fail their initial void trial, which may support the recommendation for a delayed trial without catheter.
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PURPOSE: Our goal was to review the history of the adoption of focal therapy for breast and prostate cancer and review common barriers to implementation. MATERIALS AND METHODS: A narrative review of the literature was performed of English-language MEDLINE indexed articles of breast-conservation therapy and prostate cancer focal therapy. RESULTS: The introduction of focal therapy in breast cancer began with pioneering case series, and multiple randomized trials were performed prior to widespread adoption. Focal therapy for prostate cancer has just started the process of clinical trials with a single published randomized controlled trial. Commonly cited barriers to the adoption of prostate focal therapy include historical views of Halstedian tumor biology, tumor multifocality, over-detection, limitations in prostate imaging, and trial design end points. CONCLUSIONS: The adoption of breast-conserving therapy evolved over decades and used data from multiple large, randomized, clinical trials. Barriers to the adoption of prostate cancer local therapy are similar to those faced by breast cancer clinical trials. Completion of well-designed trials in prostate cancer focal therapy is essential for its evidence-based adoption.
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Neoplasias da Mama , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Mama/terapia , Neoplasias da Próstata/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Optimal stomatal theory predicts that stomata operate to maximise photosynthesis (Anet ) and minimise transpirational water loss to achieve optimal intrinsic water-use efficiency (iWUE). We tested whether this theory can predict stomatal responses to elevated atmospheric CO2 (eCO2 ), and whether it can capture differences in responsiveness among woody plant functional types (PFTs). We conducted a meta-analysis of tree studies of the effect of eCO2 on iWUE and its components Anet and stomatal conductance (gs ). We compared three PFTs, using the unified stomatal optimisation (USO) model to account for confounding effects of leaf-air vapour pressure difference (D). We expected smaller gs , but greater Anet , responses to eCO2 in gymnosperms compared with angiosperm PFTs. We found that iWUE increased in proportion to increasing eCO2 in all PFTs, and that increases in Anet had stronger effects than reductions in gs . The USO model correctly captured stomatal behaviour with eCO2 across most datasets. The chief difference among PFTs was a lower stomatal slope parameter (g1 ) for the gymnosperm, compared with angiosperm, species. Land surface models can use the USO model to describe stomatal behaviour under changing atmospheric CO2 conditions.
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Magnoliopsida , Árvores , Árvores/fisiologia , Dióxido de Carbono/farmacologia , Cycadopsida , Folhas de Planta/fisiologia , Fotossíntese/fisiologia , Água/fisiologia , Estômatos de Plantas/fisiologiaRESUMO
Sr2NiO2Cu2Se2, comprising alternating [Sr2NiO2]2+ and [Cu2Se2]2- layers, is reported. Powder neutron diffraction shows that the Ni2+ ions, which are in a highly elongated NiO4Se2 environment with D4h symmetry, adopt a high-spin configuration and carry localized magnetic moments which order antiferromagnetically below â¼160 K in a â2a × â2a × 2c expansion of the nuclear cell with an ordered moment of 1.31(2) µB per Ni2+ ion. The adoption of the high-spin configuration for this d 8 cation in a pseudo-square-planar ligand field is supported by consideration of the experimental bond lengths and the results of density functional theory (DFT) calculations. This is in contrast to the sulfide analogue Sr2NiO2Cu2S2, which, according to both experiment and DFT calculations, has a much more elongated ligand field, more consistent with the low-spin configuration commonly found for square-planar Ni2+, and accordingly, there is no evidence for magnetic moment on the Ni2+ ions. Examination of the solid solution Sr2NiO2Cu2(Se1-x S x )2 shows direct evidence from the evolution of the crystal structure and the magnetic ordering for the transition from high-spin selenide-rich compounds to low-spin sulfide-rich compounds as a function of composition. Compression of Sr2NiO2Cu2Se2 up to 7.2 GPa does not show any structural signature of a change in the spin state. Consideration of the experimental and computed Ni2+ coordination environments and their subtle changes as a function of temperature, in addition to transitions evident in the transport properties and magnetic susceptibilities in the end members, Sr2NiO2Cu2Se2 and Sr2NiO2Cu2S2, suggest that simple high-spin and low-spin models for Ni2+ may not be entirely appropriate and point to further complexities in these compounds.
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PURPOSE: Renal function dictates sequencing and eligibility for definitive therapy in upper tract urothelial carcinoma. We investigated longitudinal glomerular filtration rate (GFR) changes after neoadjuvant chemotherapy (NAC) and nephroureterectomy (RNU). MATERIALS AND METHODS: Patients treated with ≥3 cycles of chemotherapy prior to RNU for UTUC from 2000 to 2019 were included. GFR was calculated by CKD-Epi before chemotherapy, before RNU, 1 to 3 months, and 12 months post-RNU. Pathologic stage and overall survival were compared in those with stable GFR (+/-10% of baseline) to the rest of the cohort. RESULTS: One hundred and fifty-two patients received ≥3 cycles of NAC, with 121 (79%) receiving at least 1 cycle of cisplatin. Renal function dropped by mean of 22.3 ml/min/1.73 m2 from the beginning of chemotherapy to 1-year post-surgery. In patients receiving cisplatin, a mean decline of 26.2 ml/min/1.73 m2 was observed vs. 8.8 ml/min/1.73 m2 without cisplatin-based NAC (P < 0.01). GFR after RNU was unchanged between 3 and 12 months postoperatively. At 1 to 3 months after RNU, 19% of patients had GFR<30 ml/min/1.73m2. Improvement in GFR during NAC was associated with invasive final pathologic stage (P = 0.018) and worse overall survival (P = 0.049). CONCLUSIONS: In patients managed with NAC prior to RNU, renal function stabilizes at 1 to 3 months post-operatively and remains clinically similar for cisplatin or non-cisplatin-based therapy. Improvement in GFR during NAC was associated with higher pathologic stage and poorer survival, especially in those receiving non-cisplatin-based therapy, an observation that requires further investigation.
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Carcinoma de Células de Transição , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Cisplatino/uso terapêutico , Taxa de Filtração Glomerular , Humanos , Terapia Neoadjuvante , Nefroureterectomia , Estudos Retrospectivos , Neoplasias Ureterais/tratamento farmacológico , Neoplasias Ureterais/patologia , Neoplasias Ureterais/cirurgia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by pathogenic variants in ABCD1 resulting in defective peroxisomal oxidation of very long-chain fatty acids. Most male patients develop adrenal insufficiency and one of two neurologic phenotypes: a rapidly progressive demyelinating disease in mid-childhood (childhood cerebral X-ALD, ccALD) or an adult-onset spastic paraparesis (adrenomyeloneuropathy, AMN). The neurodegenerative course of ccALD can be halted if patients are treated with hematopoietic stem cell transplantation at the earliest onset of white matter disease. Newborn screening for X-ALD can be accomplished by measuring C26:0-lysophosphatidylcholine in dried blood spots. In Nebraska, X-ALD newborn screening was instituted in July 2018. Over a period of 3.3 years, 82,920 newborns were screened with 13 positive infants detected (4 males, 9 females), giving a birth prevalence of 1:10,583 in males and 1:4510 in females. All positive newborns had DNA variants in ABCD1. Lack of genotype-phenotype correlations, absence of predictive biomarkers for ccALD or AMN, and a high proportion of ABCD1 variants of uncertain significance are unique challenges in counseling families. Surveillance testing for adrenal and neurologic disease in presymptomatic X-ALD males will improve survival and overall quality of life.
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Determining the relationship between reductions in stomatal conductance (gs ) and leaf water transport during dehydration is key to understanding plant drought responses. While numerous studies have analysed the hydraulic function of woody species, minimal research has been conducted on grasses. Here, we sought to characterize hydraulic vulnerability in five widely-occurring pasture grasses (including both C3 and C4 grasses) and determine whether reductions in gs and leaf hydraulic conductance (Kleaf ) during dehydration could be attributed to xylem embolism. Using the optical vulnerability (OV) technique, we found that all species were highly resistant to xylem embolism when compared to other herbaceous angiosperms, with 50% xylem embolism (PX50 ) occurring at xylem pressures ranging from -4.4 to -6.1 MPa. We observed similar reductions in gs and Kleaf under mild water stress for all species, occurring well before PX50 . The onset of xylem embolism (PX12 ) occurred consistently after stomatal closure and 90% reduction of Kleaf . Our results suggest that factors other than xylem embolism are responsible for the majority of reductions in gs and Kleaf during drought and reductions in the productivity of pasture species under moderate drought may not be driven by embolism.
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Secas , Embolia , Desidratação , Folhas de Planta/fisiologia , Poaceae , Xilema/fisiologiaRESUMO
Shifts in the timing, intensity and/or frequency of climate extremes, such as severe drought and heatwaves, can generate sustained shifts in ecosystem function with important ecological and economic impacts for rangelands and managed pastures. The Pastures and Climate Extremes experiment (PACE) in Southeast Australia was designed to investigate the impacts of a severe winter/spring drought (60% rainfall reduction) and, for a subset of species, a factorial combination of drought and elevated temperature (ambient +3°C) on pasture productivity. The experiment included nine common pasture and Australian rangeland species from three plant functional groups (C3 grasses, C4 grasses and legumes) planted in monoculture. Winter/spring drought resulted in productivity declines of 45% on average and up to 74% for the most affected species (Digitaria eriantha) during the 6-month treatment period, with eight of the nine species exhibiting significant yield reductions. Despite considerable variation in species' sensitivity to drought, C4 grasses were more strongly affected by this treatment than C3 grasses or legumes. Warming also had negative effects on cool-season productivity, associated at least partially with exceedance of optimum growth temperatures in spring and indirect effects on soil water content. The combination of winter/spring drought and year-round warming resulted in the greatest yield reductions. We identified responses that were either additive (Festuca), or less-than-additive (Medicago), where warming reduced the magnitude of drought effects. Results from this study highlight the sensitivity of diverse pasture species to increases in winter and spring drought severity similar to those predicted for this region, and that anticipated benefits of cool-season warming are unlikely to be realized. Overall, the substantial negative impacts on productivity suggest that future, warmer, drier climates will result in shortfalls in cool-season forage availability, with profound implications for the livestock industry and natural grazer communities.
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OBJECTIVE: To determine exposure rates to antibiotics prior to radical cystectomy and determine if there is correlation with post-operative infections. METHODS AND MATERIALS: 2248 patients were identified in the 2016 SEER-Medicare linkage who underwent radical cystectomy between 2008 and 2014 with complete prescription information. An outpatient prescription for an antibiotic within 30 days prior to cystectomy was considered exposure. Antibiotic class and combinations were recorded. Postoperative infectious diagnoses and readmissions were tabulated within 30 days of cystectomy. RESULTS: Fifty one percent of patients (n = 1149) were prescribed an outpatient antibiotic prior to cystectomy. Patients receiving antibiotics were more likely to be female (31% vs 25%, P < .01) and had been diagnosed with an infection (17% vs 11%, P < .01). Antibiotic bowel prophylaxis was prescribed to 42% of patients receiving antibiotics. Postoperatively, the exposure group had higher rates of any infection, (56% vs 51% P < .01) and UTI (36% vs 31% P < .01). All-cause readmission within 30 days was higher in the exposure cohort (26% vs 22%, P = .02) Multivariable logistic regression showed outpatient preoperative antibiotics were an independent risk factor for any infection (HR 1.19, P < .05) and readmission (hazards ratio 1.24, P = .03) in the 30 days after radical cystectomy. CONCLUSION: Outpatient antibiotic use prior to radical cystectomy is common and may be associated with increased risk of postoperative infection and readmission. Antibiotic use prior to radical cystectomy should be examined as a modifiable factor to decrease post-operative morbidity.
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Cistectomia , Neoplasias da Bexiga Urinária , Idoso , Antibacterianos/uso terapêutico , Cistectomia/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Medicare , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
INTRODUCTION: ISUP Grade Group 1 prostate cancer is the lowest histologic grade of prostate cancer with a clinically indolent course. Removal of the term 'cancer' has been proposed and has historical precedent both in urothelial and thyroid carcinoma. METHODS: Evidence-based review identifying arguments for and against Grade Group 1 being referred to as cancer. RESULTS: Grade Group 1 has histologic evidence of tissue microinvasion and 0.3-3% rate of extraprostatic extension. Genomic evaluation suggests overlap of a minority of Grade Group 1 cancers with those of Grade Group 2. Conversely, Grade Group 1 tumors appear to have distinct genetic and genomic profiles from Grade Group 3 or higher tumors. Grade Group 1 has no documented ability for regional or distant metastasis and long-term follow up after treatment or active surveillance is safe with excellent oncologic outcomes. DISCUSSION: Grade Group 1 prostate cancer, while showing evidence of neoplasia on histology has a remarkably indolent natural history more akin to non-neoplastic precursor lesions. Consideration should be given to renaming Grade Group 1 prostate cancer, which has the potential to minimize overtreatment, treatment-related side effects, patient anxiety, and financial burden on the healthcare system.
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Neoplasias da Próstata/classificação , Neoplasias da Próstata/patologia , Terminologia como Assunto , Humanos , Masculino , Gradação de TumoresRESUMO
Mistletoes are important co-contributors to tree mortality globally, particularly during droughts. In Australia, mistletoe distributions are expanding in temperate woodlands, while their hosts have experienced unprecedented heat and drought stress in recent years. We investigated whether the excessive water use of mistletoes increased the probability of xylem emboli in a mature woodland during the recent record drought that was compounded by multiple heatwaves. We continuously recorded transpiration ($T_{SLA}$) of infected and uninfected branches from two eucalypt species over two summers, monitored stem and leaf water potentials ($\Psi $) and used hydraulic vulnerability curves to estimate percent loss in conductivity (PLC) for each species. Variations in weather (vapor pressure deficit, photosynthetically active radiation, soil water content), host species and % mistletoe foliage explained 78% of hourly $T_{SLA}$. While mistletoe acted as an uncontrollable sink for water in the host even during typical summer days, daily $T_{SLA}$ increased up to 4-fold in infected branches on hot days, highlighting the previously overlooked importance of temperature stress in amplifying water loss in mistletoes. The increased water use of mistletoes resulted in significantly decreased host $\Psi _{\rm{leaf}}$ and $\Psi _{\rm{trunk}}$. It further translated to an estimated increase of up to 11% PLC for infected hosts, confirming greater hydraulic dysfunction of infected trees that place them at higher risk of hydraulic failure. However, uninfected branches of Eucalyptus fibrosa F.Muell. had much tighter controls on water loss than uninfected branches of Eucalyptus moluccana Roxb., which shifted the risk of hydraulic failure towards an increased risk of carbon starvation for E. fibrosa. The contrasting mechanistic responses to heat and drought stress between both co-occurring species demonstrates the complexity of host-parasite interactions and highlights the challenge in predicting species-specific responses to biotic agents in a warmer and drier climate.