A brief review of low-dose rate (LDR) and high-dose rate (HDR) brachytherapy boost for high-risk prostate

For patients with unfavorable or high-risk prostate cancer, dose escalated radiation therapy leads to improved progression free survival but attempts to deliver increased dose by external beam radiation therapy (EBRT) alone can be limited by late toxicities to nearby genitourinary and gastrointestinal organs at risk. Brachytherapy is a method to deliver dose escalation in conjunction with EBRT with a potentially improved late toxicity profile and improved prostate cancer related outcomes. At least three randomized controlled trials have demonstrated improved biochemical control with the addition of either low-dose rate (LDR) or high-dose rate (HDR) brachytherapy to EBRT, although only ASCENDE-RT compared brachytherapy to dose-escalated EBRT but did report an over 50% improvement in biochemical failure with a LDR boost. Multiple single institution and comparative research series also support the use of a brachytherapy boost in the DE-EBRT era and demonstrate excellent prostate cancer specific outcomes. Despite improved oncologic outcomes with a brachytherapy boost in the high-risk setting, the utilization of both LDR, and HDR brachytherapy use is declining. The acute genitourinary toxicities when brachytherapy boost is combined with EBRT, particularly a LDR boost, are of concern in comparison to EBRT alone. HDR brachytherapy boost has many physical properties inherent to its rapid delivery of a large dose which may reduce acute toxicities and also appeal to the radiobiology of prostate cancer. We herein review the evidence for use of either LDR or HDR brachytherapy boost for high-risk prostate cancer and summarize comparisons between the two treatment modalities

Update on perineuronal net staining with Wisteria floribunda agglutinin (WFA)

As chemically specialized forms of the extracellular matrix in the central nervous system, polyanionic perineuronal nets (PNs) contain diverse constituents, including chondroitin sulfate proteoglycans (CSPGs), hyaluronic acid, and tenascins. They are detectable by various histological approaches such as colloidal iron binding and immunohistochemical staining to reveal, for instance, the CSPGs aggrecan, neurocan, phosphacan, and versican. Moreover, biotin, peroxidase, or fluorescein conjugates of the lectins Vicia villosa agglutinin and soybean agglutinin enable the visualization of PNs. At present, the N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA) is the most widely applied marker for PNs. Therefore, this article is largely focused on methodological aspects of WFA staining. Notably, fluorescent WFA labeling allows, after its conversion into electron-dense adducts, electron microscopic analyses. Furthermore, the usefulness of WFA conjugates for the oftentimes neglected in vivo and in vitro labeling of PNs is emphasized. Subsequently, we discuss impaired WFA-staining sites after long-lasting experiments in vitro, especially in autoptic brain samples with long postmortem delay and partial enzymatic degradation, while immunolabeling of aggrecan and CSPG link proteins under such conditions has proven more robust. In some hippocampal regions from perfusion-fixed mice, more PNs are aggrecan immunoreactive than WFA positive, whereas the retrosplenial cortex displays many WFA-binding PNs devoid of visible aggrecan immunoreactivity. Additional multiple fluorescence labeling exemplarily revealed in ischemic tissue diminished staining of WFA-binding sites and aquaporin 4 and concomitantly upregulated immunolabeling of neurofilament, light chains, and collagen IV. Finally, we briefly discuss possible future staining approaches based on nanobodies to facilitate novel technologies revealing details of net morphology

Treatment patterns and overall survival outcomes among patients aged 80 yr or older with high-risk prostate cancer

BACKGROUND: Elderly patients diagnosed with high-risk prostate cancer (PCa) present a therapeutic dilemma of balancing treatment of a potentially lethal malignancy with overtreatment of a cancer that may not threaten life expectancy. OBJECTIVE: To investigate treatment patterns and overall survival outcomes in this group of patients. DESIGN SETTING AND PARTICIPANTS: A retrospective cohort study was conducted. We queried the National Cancer Database for high-risk PCa in patients aged 80 yr or older diagnosed during 2004-2016. INTERVENTION: Eligible patients underwent no treatment following biopsy (ie, observation), androgen deprivation therapy (ADT) alone, radiation therapy (RT) alone, RT + ADT, or surgery. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier, log rank, and multivariate Cox proportional hazard regression was performed to compare overall survival (OS). RESULTS AND LIMITATIONS: A total of 19 920 men were eligible for analysis, and the most common treatment approach was RT + ADT (7401 patients; 37.2%). Observation and ADT alone declined over time (59.3% in 2004 vs 47.5% in 2016). There was no observed difference in OS between observation and ADT alone (adjusted hazard ratio [HR] 1.04, 95% confidence interval [CI], 0.99-1.09; CONCLUSIONS: This analysis demonstrates that the use of definitive local therapy, including surgery or RT ± ADT, is increasing and is associated with a 50% reduction in overall mortality compared with observation or ADT alone. While prospective validation is warranted, elderly men with high-risk disease eligible for definitive management should be counseled on the risks, including a possible compromise in OS, with deferring definitive management. PATIENT SUMMARY: Elderly men are more often diagnosed with higher-risk prostate cancer but are less likely to receive curative treatment options than younger men. Our analysis demonstrates that for men ≥80 yr of age with high-risk prostate cancer, definitive local therapy, including surgery or radiation therapy and/or androgen deprivation therapy, is associated with a 50% reduction in overall mortality compared with observation or androgen deprivation therapy alone. We therefore recommend that life expectancy (ie, physiologic age) be taken into account, over chronologic age, and that elderly men with good life expectancy (eg, \u3e5 yr; minimal comorbidity) should be offered definitive, life-prolonging therapy

Simulation of thermal conductivity and heat transport in solids

Using molecular dynamics (MD) with classical interaction potentials we present calculations of thermal conductivity and heat transport in crystals and glasses. Inducing shock waves and heat pulses into the systems we study the spreading of energy and temperature over the configurations. Phonon decay is investigated by exciting single modes in the structures and monitoring the time evolution of the amplitude using MD in a microcanonical ensemble. As examples, crystalline and amorphous modifications of Selenium and $\rm{SiO_2}$ are considered.Comment: Revtex, 8 pages, 11 postscript figures, accepted for publication in PR

Geochemistry of Carbonates on Mars: Implications for Climate History and Nature of Aqueous Environments

Ongoing research on martian meteorites and a new set of observations of carbonate minerals provided by an unprecedented series of robotic missions to Mars in the past 15 years help define new constraints on the history of martian climate with important crosscutting themes including: the CO_2 budget of Mars, the role of Mg-, Fe-rich fluids on Mars, and the interplay between carbonate formation and acidity. Carbonate minerals have now been identified in a wide range of localities on Mars as well as in several martian meteorites. The martian meteorites contain carbonates in low abundances (<1 vol.%) and with a wide range of chemistries. Carbonates have also been identified by remote sensing instruments on orbiting spacecraft in several surface locations as well as in low concentrations (2–5 wt.%) in the martian dust. The Spirit rover also identified an outcrop with 16 to 34 wt.% carbonate material in the Columbia Hills of Gusev Crater that strongly resembled the composition of carbonate found in martian meteorite ALH 84001. Finally, the Phoenix lander identified concentrations of 3–6 wt.% carbonate in the soils of the northern plains. The carbonates discovered to date do not clearly indicate the past presence of a dense Noachian atmosphere, but instead suggest localized hydrothermal aqueous environments with limited water availability that existed primarily in the early to mid-Noachian followed by low levels of carbonate formation from thin films of transient water from the late Noachian to the present. The prevalence of carbonate along with evidence for active carbonate precipitation suggests that a global acidic chemistry is unlikely and a more complex relationship between acidity and carbonate formation is present

Effectiveness of postoperative radiotherapy after radical cystectomy for locally advanced bladder cancer

BACKGROUND: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. METHODS: We identified ≥ pT3pN0-3M0 LABC patients in the National Cancer Database diagnosed 2004-2014 who underwent RC ± PORT. OS was calculated using Kaplan-Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. RESULTS: 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2-21.8) for PORT vs 20.8 months (95% CI, 20.3-21.3) for no PORT (P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78-0.97); P = 0.008. A one-to-three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity-matched cohort, median OS was 19.8 months (95% CI, 18.0-21.6) for PORT vs 16.9 months (95% CI, 15.6-18.1) for no PORT (P = 0.030). In the propensity-matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins (P \u3c 0.01 all). CONCLUSION: In this observational cohort, PORT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of PORT in selected patients with LABC, regardless of histology. Prospective trials of PORT are warranted

Acute effects of mixed circuit training on hemodynamic and cardiac autonomic control in chronic hemiparetic stroke patients: a randomized controlled crossover trial

Objectives: To investigate whether a single bout of mixed circuit training (MCT) can elicit acute blood pressure (BP) reduction in chronic hemiparetic stroke patients, a phenomenon also known as post-exercise hypotension (PEH). Methods: Seven participants (58 ± 12 years) performed a non-exercise control session (CTL) and a single bout of MCT on separate days and in a randomized counterbalanced order. The MCT included 10 exercises with 3 sets of 15-repetition maximum per exercise, with each set interspersed with 45 s of walking. Systolic (SBP) and diastolic (DBP) blood pressure, mean arterial pressure (MAP), cardiac output (Q), systemic vascular resistance (SVR), baroreflex sensitivity (BRS), and heart rate variability (HRV) were assessed 10 min before and 40 min after CTL and MCT. BP and HRV were also measured during an ambulatory 24-h recovery period. Results: Compared to CTL, SBP (∆-22%), DBP (∆-28%), SVR (∆-43%), BRS (∆-63%), and parasympathetic activity (HF; high-frequency component: ∆-63%) were reduced during 40 min post-MCT (p < 0.05), while Q (∆35%), sympathetic activity (LF; low-frequency component: ∆139%) and sympathovagal balance (LF:HF ratio: ∆145%) were higher (p < 0.001). In the first 10 h of ambulatory assessment, SBP (∆-7%), MAP (∆-6%), and HF (∆-26%) remained lowered, and LF (∆11%) and LF:HF ratio (∆13%) remained elevated post-MCT vs. CTL (p < 0.05). Conclusion: A single bout of MCT elicited prolonged PEH in chronic hemiparetic stroke patients. This occurred concurrently with increased sympathovagal balance and lowered SVR, suggesting vasodilation capacity is a major determinant of PEH in these patients. This clinical trial was registered in the Brazilian Clinical Trials Registry (RBR-5dn5zd), available at https://ensaiosclinicos.gov.br/rg/RBR-5dn5zd. Clinical Trial Registration: https://ensaiosclinicos.gov.br/rg/RBR-5dn5zd, identifier RBR-5dn5z

OA011-03. Clusterin, a natural ligand of DC-SIGN present in human semen inhibits HIV capture and transmission by dendritic cells

International audiencen.

The derivation of the formyl-group oxygen of chlorophyll b in higher plants from molecular oxygen.

The mechanism of formation of the formyl group of chlorophyll b has long been obscure but, in this paper, the origin of the 7-formyl-group oxygen of chlorophyll b in higher plants was determined by greening etiolated maize leaves, excised from dark-grown plants, by illumination under white light in the presence of either H218O or 18O2 and examining the newly synthesized chlorophylls by mass spectroscopy. To minimize the possible loss of 18O label from the 7-formyl substituent by reversible formation of chlorophyll b-71-gem-diol (hydrate) with unlabelled water in the cell, the formyl group was reduced to a hydroxymethyl group during extraction with methanol containing NaBH4: chlorophyll a remained unchanged during this rapid reductive extraction process. Mass spectra of chlorophyll a and [7-hydroxymethyl]-chlorophyll b extracted from leaves greened in the presence of either H218O or 18O2 revealed that 18O was incorporated only from molecular oxygen but into both chlorophylls: the mass spectra were consistent with molecular oxygen providing an oxygen atom not only for incorporation into the 7-formyl group of chlorophyll b but also for the well-documented incorporation into the 131-oxo group of both chlorophylls a and b [see Walker, C. J., Mansfield, K. E., Smith, K. M. & Castelfranco, P. A. (1989) Biochem. J. 257, 599–602]. The incorporation of isotope led to as much as 77% enrichment of the 131-oxo group of chlorophyll a: assuming identical incorporation into the 131 oxygen of chlorophyll b, then enrichment of the 7-formyl oxygen was as much as 93%. Isotope dilution by re-incorporation of photosynthetically produced oxygen from unlabelled water was negligible as shown by a greening experiment in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The high enrichment using 18O2, and the absence of labelling by H218O, unequivocally demonstrates that molecular oxygen is the sole precursor of the 7-formyl oxygen of chlorophyll b in higher plants and strongly suggests a single pathway for the formation of the chlorophyll b formyl group involving the participation of an oxygenase-type enzyme