Enzymatic Synthesis of α-Glucosyl-Baicalin through Transglucosylation via Cyclodextrin Glucanotransferase in Water.

Baicalin is a biologically active flavone glucuronide with poor water solubility that can be enhanced via glucosylation. In this study, the transglucosylation of baicalin was successfully achieved with CGTases from Thermoanaerobacter sp. and Bacillus macerans using α-cyclodextrin as a glucosyl donor. The synthesis of baicalin glucosides was optimized with CGTase from Thermoanaerobacter sp. Enzymatically modified baicalin derivatives were α-glucosylated with 1 to 17 glucose moieties. The two main glucosides were identified as Baicalein-7-O-α-D-Glucuronidyl-(1→4')-O-α-D-Glucopyranoside (BG1) and Baicalein-7-O-α-D-Glucuronidyl-(1→4')-O-α-D-Maltoside (BG2), thereby confirming recent findings reporting that glucuronyl groups are acceptors of this CGTase. Optimized conditions allowed for the attainment of yields above 85% (with a total glucoside content higher than 30 mM). BG1 and BG2 were purified via centrifugal partition chromatography after an enrichment through deglucosylation with amyloglucosidase. Transglucosylation increased the water solubility of BG1 by a factor of 188 in comparison to that of baicalin (molar concentrations), while the same value for BG2 was increased by a factor of 320. Finally, BG1 and BG2 were evaluated using antioxidant and anti-glycation assays. Both glucosides presented antioxidant and anti-glycation properties in the same order of magnitude as that of baicalin, thereby indicating their potential biological activity.

Findings on Diagnostic Magnetic Resonance Imaging Before Radiotherapy for Prostate Cancer.

PURPOSE: Pre-treatment diagnostic magnetic resonance imaging (MRI) is used in prostate cancer detection and staging; however, little is known about its potential for radiotherapy treatment decision, or its prognostic value. We investigated the findings on pre-treatment MRI and its potential influence on treatment decisions, and its ability to predict biochemical recurrence in patients treated with radiotherapy. METHODS: Files of patients treated by radiotherapy from 2014 to 2022 were searched for if they had had an MRI within 12 months before radiotherapy. Prostate Imaging Reporting & Data System (PI-RADS) score, index lesion diameter and the presence of organ confined disease or extra-prostatic extension were correlated with their Cancer of the Prostate Risk Assessment (CAPRA) score. Distribution of radiological and clinical features between groups were estimated using a chi-squared test. RESULTS: Out of 1280 patients, 314 (24.5%) had an MRI. The distribution depended on the treatment received: 22.5% who received low-dose rate (LDR) brachytherapy as monotherapy, 24.0% treated with high-dose rate (HDR) boost and 32.0% treated with external-beam radiotherapy (EBRT) (P = .017). The CAPRA score significantly correlated with the PI-RADS score (r = .342, P < .01) and the diameter of the index lesion (r = .473, P < .01). A clinically significant number of 22% patients with CAPRA ≤ 3 disease presented with lesions ≥15 mm and were less likely to be treated with LDR monotherapy (P < .01). 39 patients had a recurrence, only 5 had an MRI: 4 had a lesion of ≥20 mm and 3 a seminal vesicle invasion. CONCLUSION: More than twenty percent of patients with CAPRA ≤3 presented on MRI a ≥15 mm lesion. An MRI could potentially affect treatment choice, and although exploratory our results suggest an important prognostic potential.

Prevalence and Risk Factors of QTc Prolongation in Prostate Cancer Patients Undergoing Brachytherapy.

QTc prolongation is linked to Torsade de Pointes, sudden cardiac death, and overall cardiovascular mortality. 754 prostate cancer patients undergoing brachytherapy were analyzed, prolonged QTc was defined as ≥450ms. A prolonged QTc was more frequent (10.1 vs. 5.1%, p = 0.040) in patients with high-risk cancer than in low to intermediate risk patients. The absolute QTc-time was correlated with age (r = 0.125), neutrophil count (r = 0.130) and negatively correlated with the testosterone level (r=-0.205). Treating physicians should be aware of this and monitor the QTc during ADT to possibly decrease cardiac morbidity/mortality in these patients who are more likely to require ADT.

Overall renewal of skin lipids with Vetiver extract for a complete anti-ageing strategy.

OBJECTIVE: Skin lipids are essential in every compartment of the skin where they play a key role in various biological functions. Interestingly, their role is central in the maintenance of hydration which is related to skin barrier function and in the skin structure through adipose tissue. It is well described today that skin lipids are affected by ageing giving skin sagging, wrinkles and dryness. Thereby, developing cosmetic actives able to reactivate skin lipids would be an efficient ant-ageing strategy. Due to the strong commitment of our scientists to innovate responsibly and create value, they designed a high value active ingredient named here as Vetiver extract, using a ground-breaking upcycling approach. We evidenced that this unique extract was able to reactivate globally the skin lipids production, bringing skin hydration and plumping effect for mature skin. METHOD: In order to demonstrate the global renewal of lipids, we evaluated the lipids synthesis on cutaneous cells that produce lipids such as keratinocytes, sebocytes and adipocytes then on Reconstructed Human Epidermis and skin explants. We evaluated the expression of proteins involved in ceramides transport and barrier cornification. We then evaluated hydration and sebaceous parameters on a panel of mature volunteers. RESULTS: We firstly demonstrated that Vetiver extract induced sebum production from human sebocytes cells lines but also improved its quality as observed by the production of specific antimicrobial lipids. Secondly, we demonstrated that Vetiver extract was able to restore skin barrier with the increase of skin lipids neosynthesis on Reconstructed Human Epidermis and skin explants. We also evidenced that Vetiver extract stimulated the lipids transport and epidermal cornification. Finally, Vetiver extract showed a significant effect on adipogenesis and maturation of adipocytes at in vitro and ex vivo models. We confirmed all these activities by showing that Vetiver extract improved sebum production and brought hydration through an increase of lipids content and their conformation. Vetiver extract induced an improvement of skin fatigue and a plumping effect by acting deeply on adipose tissue. CONCLUSION: In conclusion, we developed an active ingredient able to bring anti-ageing effect for mature skin by a global increase of skin lipids.

OBJECTIF: Les lipides de la peau sont essentiels dans chaque compartiment de la peau où ils jouent un rôle clé dans diverses fonctions biologiques. Il est intéressant de noter que leur rôle est central dans le maintien de l'hydratation, liée à la fonction de barrière cutanée, mais aussi dans la structure même de la peau, par le biais du tissu adipeux. Il est bien décrit aujourd'hui que les lipides de la peau sont affectés par le vieillissement, ce qui entraîne un relâchement de la peau, des rides et une sécheresse. Ainsi, le développement d'actifs cosmétiques capables de réactiver les lipides de la peau serait une stratégie efficace de lutte contre le vieillissement. En raison de l'engagement fort de nos scientifiques à innover de manière responsable et à créer de la valeur, ils ont conçus un ingrédient actif à forte valeur ajoutée, appelé ici extrait de Vétiver, en utilisant une approche révolutionnaire de « up-cycling ¼. Nous avons démontré que cet extrait unique était capable de réactiver globalement la production de lipides de la peau, apportant une hydratation de la peau et un effet repulpant pour les peaux matures. MÉTHODES: Afin de démontrer le renouvellement global des lipides, nous avons évalué la synthèse des lipides sur les cellules cutanées qui produisent des lipides tels que les kératinocytes, les sébocytes et les adipocytes, puis sur un modèle d'Epiderme Humain Reconstruit et les explants de peau. Nous avons évalué l'expression des protéines impliquées dans le transport des céramides et la kératinisation de la barrière cutanée. Nous avons ensuite évalué l'hydratation et les paramètres sébacés sur un panel de volontaires matures. RÉSULTATS: Nous avons tout d'abord démontré que l'extrait de Vétiver induit la production de sébum à partir de lignées cellulaires de sébocytes humains mais améliore également sa qualité comme l'indique la production de lipides antimicrobiens spécifiques. Ensuite, nous avons démontré que l'extrait de Vétiver était capable de restaurer la barrière cutanée grâce à l'augmentation de la néosynthèse lipidique sur un modèle d'Epiderme Humain Reconstruit et sur des explants de peau. Nous avons également démontré que l'extrait de Vétiver stimulait le transport des lipides et la kératinisation de l'épiderme. Enfin, l'extrait de Vétiver a montré un effet significatif sur l'adipogenèse et la maturation des adipocytes dans des modèles in vitro et ex vivo. Nous avons confirmé à l'échelle clinique toutes ces activités en montrant que l'extrait de Vétiver améliorait la production de sébum et apportait une hydratation grâce à une augmentation de la teneur en lipides ainsi qu'une modification de leur conformation. L'extrait de Vétiver a induit une amélioration de la fatigue cutanée et un effet repulpant en agissant en profondeur sur le tissu adipeux. CONCLUSION: En conclusion, nous avons développé un ingrédient actif capable d'apporter un effet anti-âge aux peaux matures par une augmentation globale des lipides de la peau.

Screening for tyrosinase inhibitors from actinomycetes; identification of trichostatin derivatives from Streptomyces sp. CA-129531 and scale up production in bioreactor.

In the course of a primary screening of 614 microbial actinomycete extracts for the discovery of tyrosinase inhibitors, the EtOAc extract of the fermentation broth of the strain Streptomyces sp. CA-129531 isolated from a Martinique sample, exhibited in cell free and cell-based assays the most promising activity (IC50 value of 63 µg/mL). Scaled-up production in a bioreactor led to the isolation of one new trichostatic acid analogue, namely trichostatic acid B (1), along with six known trichostatin derivatives (2-7), four diketopiperazines (8-11), two butyrolactones (12-13) and one hydroxamic acid siderophore (14). Among them, trichostatin A (4) showed a Ki value of 6.1 µM and six times stronger anti-tyrosinase activity (IC50 2.18 µΜ) than kojic acid (IC50 14.07 µΜ) used as a positive control. Deoxytrichostatin A (6) displayed also strong inhibitory activity against tyrosinase (IC50 19.18 µΜ). Trichostatin A production in bioreactor started together with the exponential phase of growth (day 4) and the maximum concentration was reached at day 9 (2.67 ± 0.13 µg/mL). Despite the cytotoxicity of some individual components, the EtOAc extract showed no cytotoxic effect on HepG2, A2058, A549, MCF-7 and MIA PaCa-2 cell lines, (IC50 >2.84 mg/mL) and against BG fibroblasts at the concentrations where the whitening effect was exerted, reassuring its safety and great tyrosinase inhibitory potential.

The relationship between pre-radiation therapy testosterone levels and prostate cancer aggressiveness.

We investigated whether there is an association between testosterone levels and prostate cancer aggressiveness in patients treated with radiation therapy who underwent a prostatectomy or prostate radiotherapy (EBRT). A total of 380 patients who received primary or post-operative radiotherapy were identified. At the time of radiotherapy, baseline testosterone levels and body mass index (BMI) measurements were available. On multivariate analysis (MVA), higher prostate-specific antigen (PSA) levels were predictive of testosterone ≥10.4  (OR = 1.3, p = .04) and testosterone ≥12.0 nmol/L (OR = 1.3, p = .04). Patients with a Gleason score ≥8 were more likely to have testosterone <8 nmol/L than patients with a lower score (31% vs. 20%, p = .043). On univariate analysis, a Gleason score ≥8 was associated with a lower likelihood of having a normal (≥8 nmol/L) testosterone level (OR = 0.51, 95% CI: 0.3-0.9, p = .02), and on MVA adjusted for post-surgical versus primary EBRT and BMI (≥30 kg/m2 ), the Gleason score lost its statistical significance (p = .09). While higher PSA levels are associated with higher testosterone levels, the interaction between Gleason score and testosterone is unclear and merits further study.

Pre-radiotherapy PSA progression is a negative prognostic factor in prostate cancer patients using 5­alpha-reductase inhibitors.

OBJECTIVE: To investigate the impact of 5­alpha-reductase inhibitor (5-ARI) use on radiotherapy outcomes for localized prostate cancer. PATIENTS AND METHODS: We included 203 patients on a 5-ARI from our institutional database comprising over 2500 patients who had been treated with either external beam radiotherapy (EBRT) or brachytherapy for localized prostate cancer. Patients received a 5-ARI for urinary symptoms or active surveillance. Cancer progressions at the time of definitive treatment were analyzed according to the following criteria: (a) progression of Gleason score or increase in cancer volume on biopsy, (b) first biopsy positive for cancer after being treated for urinary symptoms with a 5-ARI, and (c) prostate-specific antigen (PSA) progression with or without a previous cancer diagnosis. Biochemical failure (BF) was defined by the Phoenix definition. Log-rank test was used for survival analysis. RESULTS: At a median follow-up of 38.2 months (standard deviation 22.2 months), 10 (4.9%) patients experienced BF. Concerning prostate cancer progression criteria, 52% of men demonstrated none, 37% showed only one criterion, and 11% showed two. Using univariate analysis, PSA progression (p = 0.004) and appearance of a positive biopsy (p < 0.001) were significant predictive factors for BF, while Gleason progression (p = 0.3) was not. In multivariate analysis adjusted for cancer aggressiveness, rising PSA (hazard ratio, HR, 5.7; 95% confidence interval, CI, 1.1-28.8; p = 0.04) and the number of cancer progression factors (HR 2.9, 95% CI 1.2-7.0, p = 0.02) remained adverse risk factors. CONCLUSION: PSA progression experienced during 5­ARI treatment before radiotherapy is predictive of worse biochemical outcome. Such details should be considered when counseling men prior to radiation therapy.

Reconstruction of HMBC Correlation Networks: A Novel NMR-Based Contribution to Metabolite Mixture Analysis.

A new in silico method is introduced for the dereplication of natural metabolite mixtures based on HMBC and HSQC spectra that inform about short-range and long-range H-C correlations occurring in the carbon skeleton of individual chemical entities. Starting from the HMBC spectrum of a metabolite mixture, an algorithm was developed in order to recover individualized HMBC footprints of the mixture constituents. The collected H-C correlations are represented by a network of NMR peaks connected to each other when sharing either a 1H or 13C chemical shift value. The network obtained is then divided into clusters using a community detection algorithm, and finally each cluster is tentatively assigned to a molecular structure by means of a NMR chemical shift database containing the theoretical HMBC and HSQC correlation data of a range of natural metabolites. The proof of principle of this method is demonstrated on a model mixture of 3 known natural compounds and then on a real-life bark extract obtained from the common spruce (Picea abies L.).

Impact of diabetes and metformin use on prostate cancer outcome of patients treated with radiation therapy: results from a large institutional database.

INTRODUCTION: Conflicting data exists on the influence of metformin on prostate cancer. We investigated the importance of metformin in patients treated with radiotherapy or brachytherapy. MATERIALS AND METHODS: All patients from a large institutionalized database, treated for primary localized prostate cancer with either brachytherapy or external-beam radiotherapy ± androgen deprivation therapy were identified. Groups were compared by Kaplan-Meier analyses and Cox regression models. Multivariate analysis was adjusted for CAPRA-Score, type of treatment and age. RESULTS: A total of 2441 patients with complete data was identified. Among the 382 patients (16% of total) were diabetic. Two-hundred and eighty-one of the 382 diabetics (74%) were treated with metformin and 101 were treated with other anti-diabetic medication. Median follow up was 48 months (interquartile range [IQR] 24-84). Two-hundred eighteen patients (9%) died and 150 (6%) experienced biochemical recurrence (BCR). On unadjusted univariate analysis for BCR-free survival, metformin users showed a 50% reduction in BCR compared to non-metformin users. The results remained significant on multivariate analysis comparing diabetic metformin users to non-metformin users (diabetics and non-diabetics combined) (hazard ratio [HR] 0.5-0.6, p = 0.03-0.04) but lost its significance when adjusting for cancer aggressiveness. On multivariate analysis, diabetics had worse overall survival (OS) than non-diabetics (HR 1.5, 95% confidence interval [CI] 1.08-2.06, p = 0.01), but diabetics on metformin fared better than diabetics not taking metformin (HR 0.5, 95% CI 0.26-0.86, p = 0.01). CONCLUSION: Metformin use in this analysis appears to be associated with better BCR and OS. Larger datasets and prospective trials are warranted to validate these results.

GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization.

The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae). Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A) and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR). An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA)-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1) receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC) and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus marinus extract. Two active molecules, namely, γ-aminobutyric acid (GABA) and its structural derivative GABA-alanine, demonstrated a strong capacity to positively regulate skin sensitization mechanisms related to the TRPV1 receptors under PMA-induced inflammatory conditions, therefore providing interesting perspectives for the treatment of sensitive skins, atopia, dermatitis, or psoriasis.

External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer.

BACKGROUND: Previous studies have examined testosterone levels after external beam radiation (EBRT) monotherapy, but since 2002 only sparse contemporary data have been reported. AIM: To examine testosterone kinetics in a large series of contemporary patients after EBRT. METHODS: The study was conducted in 425 patients who underwent definitive EBRT for localized prostate cancer from 2002 through 2014. Patients were enrolled in several phase II and III trials. Exclusion criteria were neoadjuvant or adjuvant androgen-deprivation therapy or missing data. Testosterone was recorded at baseline and then according to each study protocol (not mandatory in all protocols). Statistical analyses consisted of means and proportions, Kaplan-Meier plots, and logistic and Cox regression analyses. OUTCOMES: Testosterone kinetics after EBRT monotherapy and their influence on biochemical recurrence. RESULTS: Median follow-up of 248 assessable patients was 72 months. One hundred eighty-six patients (75.0%) showed a decrease in testosterone. Median time to first decrease was 6.4 months. Median percentage of decrease to the nadir was 30% and 112 (45.2%) developed biochemical hypogonadism (serum testosterone < 8 nmol/L). Of all patients with testosterone decrease, 117 (62.9%) recovered to at least 90% of baseline levels. Advanced age, increased body mass index, higher baseline testosterone level, and lower nadir level were associated with a lower chance of testosterone recovery. Subgroup analyses of 166 patients treated with intensity-modulated radiotherapy confirmed the results recorded for the entire cohort. In survival analyses, neither testosterone decrease nor recovery was predictive for biochemical recurrence. CLINICAL IMPLICATIONS: EBRT monotherapy influences testosterone kinetics, and although most patients will recover, approximately 45% will have biochemical hypogonadism. STRENGTHS AND LIMITATIONS: We report on the largest contemporary series of patients treated with EBRT monotherapy in whom testosterone kinetics were ascertained. Limitations are that testosterone follow-up was not uniform and the study lacked information on health-related quality-of-life data. CONCLUSION: Our findings indicate that up to 75% of patients will have a profound testosterone decrease, with up to a 40% increase in rates of biochemical hypogonadism, although the latter events will leave biochemical recurrence unaffected. Pompe RS, Karakrewicz PI, Zaffuto E, et al. External Beam Radiotherapy Affects Serum Testosterone in Patients With Localized Prostate Cancer. J Sex Med 2017;14:876-882.

Comparison of external beam radiotherapy versus permanent seed brachytherapy as monotherapy for intermediate-risk prostate cancer - a single center Canadian experience.

INTRODUCTION: We tested different classification systems in order to separate intermediate-risk prostate cancers into prognostic groups. We then examined which groups were most suited for either prostate seed brachytherapy (PB) or external beam radiotherapy (EBRT). MATERIALS AND METHODS: We selected patients with D'Amico intermediate-risk prostate cancer who were treated exclusively with either PB or EBRT. Patients were excluded if they had received androgen deprivation therapy in combination with EBRT or a follow up of < 30 months without recurrence. The Kaplan-Meier method was used to compare groups. RESULTS: Our sample consisted of 475 patients treated from July 2002-September 2013. Median follow up for patients without biochemical failure (BF) was 56 months (interquartile range 44-78); 222 patients (47%) were treated with PB exclusively (D90 interquartile range 145-176 Gy) and 253 (53%) with EBRT exclusively (dose interquartile range 76-80 Gy). The rate of BF was significantly lower in patients treated with PB (5.4%) than in patients treated with EBRT (14.2%) (p = 0.036, log-rank test). Upon univariate analysis, significant predictors of BF included the number of unfavorable intermediate-risk factors (0, 1, 2, 3) (p = 0.024) as well as the Cancer of the Prostate Risk Assessment (CAPRA) score (p = 0.002). After adjusting for the type of treatment, only the CAPRA score remained predictive (p = 0.025). For patients with a CAPRA score of 0-2, those with PB fared better than those treated with EBRT (p = 0.042). This difference disappeared in patients with a CAPRA score of 3-5 (p = 0.5). CONCLUSIONS: Using our current selection criteria for monotherapy, we found that PB or EBRT as monotherapy are equally effective treatment options for intermediate-risk prostate cancer.

Assessment of function and quality of life in a phase II multi-institutional clinical trial of fractionated simultaneous in-field boost radiotherapy for patients with 1-3 metastases.

We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Eighty seven people with 1-3 brain metastases (54/87 lung primary, 42/87 single brain metastases) were enrolled on this Phase II trial of WBRT (30 Gy/10) + simultaneous FSRT, (60 Gy/10). Median overall follow-up and survival was 5.4 months, 6 month actuarial intra-lesional control was 78 %; only 1 patient exhibited grade 4 toxicity (worsened seizures); most treatment related toxicity was grade 1 or 2; 2/87 patients demonstrated asymptomatic radiation necrosis on follow-up imaging. Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (>10 points decrease from baseline for KPS and FACT-Br, MMSE fall to <27) ranged from 26 to 38 % for KPS, 32-59 % for FACT-Br and 0-16 % for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (≤6 months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. The effects on function and quality of life of this integrated treatment of WBRT + simultaneous FSRT were similar to other published series combining WBRT + radiosurgery.

Optimizing subcutaneous injection of the gonadotropin-releasing hormone receptor antagonist degarelix.

The gonadotropin-releasing hormone (GnRH) receptor antagonist degarelix has several unique characteristics compared to luteinizing hormone-releasing hormone (LHRH) analogs used in the management of prostate cancer. Notable differences of GnRH receptor antagonists include no flare reaction, and a more rapid suppression of testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) and prostate-specific antigen (PSA) compared to LHRH analogs. Despite emerging evidence supporting the use of GnRH receptor antagonists over the more widely used LHRH analogs in the management of prostate cancer, physicians may be reluctant to prescribe degarelix. They may be concerned about patient complaints about injection-site reactions (ISRs). The subcutaneous injection of degarelix has been associated with a higher rate of ISRs compared with the intramuscular injections of LHRH analogs. This "How I Do It" article describes techniques and strategies that have been developed by physicians and nurses to reduce the discomfort associated with the subcutaneous delivery of degarelix.

Risk factors for PSA bounce following radiotherapy: outcomes from a multi-modal therapy analysis.

INTRODUCTION: To identify risk factors for PSA bounce (PSAb) and compare characteristics of prostate cancer patients treated with brachytherapy and external beam radiotherapy (EBRT). MATERIALS AND METHODS: We identified 362 patients treated for low risk prostate adenocarcinoma (D'Amico criteria) with a follow up time of at least 36 months. Patients received either: 1) EBRT 76 Gy in 38 fractions (n = 58); 2) hypofractionated EBRT, 45 Gy in 9 once-weekly fractions (n = 74); 3) seed brachytherapy (n = 230). PSAb was defined as a rise >= 0.2 ng/mL with subsequent return to baseline within the first 3 years after treatment. Univariate and multivariate logistic regression models were estimated to assess the association between clinical factors and occurrence of PSAb. RESULTS: There was no significant difference between treatment groups (p = 0.349), with an overall PSAb rate of 28.5%. Upon univariate analysis, the following were predictive of a lower PSAb rate: older age (OR = 0.96), higher PSA at diagnosis (OR = 0.87), more positive biopsy cores (OR = 0.98), and a higher Cancer of the Prostate Risk Assessment (CAPRA) score (CAPRA of 3 versus 1: OR = 0.33). Multivariate analysis confirmed the significance of fewer positive biopsy cores (OR = 0.99) and a lower CAPRA score (CAPRA 3 versus 1: OR = 0.34). These factors also predicted a shorter time to first PSAb. CONCLUSIONS: We found comparable rates of PSAb after different regimens of radiotherapy. We hypothesize that it results from late damage to healthy prostatic tissue. This idea is supported by the fact that we found that clinical factors indicative of a lower tumor burden were predictive of a PSAb.

A highly soluble form of rutin for instant resolution of mask-wearing related disorders.

BACKGROUND: The COVID-19 pandemic brought about a new normal, necessitating the use of personal protective equipment (PPE) like face shields, surgical masks, gloves, and goggles. However, prolonged mask-wearing introduced skin-related issues due to changes in the skin's microenvironment, including increased humidity and temperature, as well as pressure on the skin. These factors led to skin deformation, vascular issues, edema, and inflammation, resulting in discomfort and cosmetic concerns. Clinical reports quickly highlighted the consequences of long-term mask use, including increased cases of "maskne" (mask-related acne) or mask-wearing related disorders such as rosacea flare-ups, skin-barrier defects, itching, erythema, redness, hyperpigmentation, and lichenification. Some of these issues, like inflammation, oxidative stress, and poor wound healing, could be directly linked to acne-related disorders or skin hypoxia. AIM: To address these problems, researchers turned to rutin, a well-known flavonoid with antioxidant, vasoactive, and anti-inflammatory properties. However, rutin's poor water solubility presented a challenge for cosmetic formulations. To overcome this limitation, a highly water-soluble form of rutin was developed, making it suitable for use at higher concentrations. METHODS: In vitro and ex vivo tests were conducted, as well as an innovative clinical trial including volunteers wearing surgical masks for at least 2 h, to evaluate the biological activity of this soluble rutin on the main skin concerns associated with mask-wearing (inflammation, oxidative stress, skin repair, hyperpigmentation, and skin redness). RESULTS: The in vitro results showed that the active ingredient significantly reduced oxidative stress, improved wound healing, and reduced inflammation. In dark skin explants, the active ingredient significantly reduced melanin content, indicating its lightening activity. This effect was confirmed in the clinical study, where brown spots decreased significantly after 4 days of application. Moreover, measurements on volunteers demonstrated a decrease in skin redness and vascularization after the active ingredient application, indicating inflammation and erythema reduction. Volunteers reported improved skin comfort. CONCLUSION: In summary, the COVID-19 pandemic led to various skin issues associated with mask-wearing. A highly soluble form of rutin was developed, which effectively addressed these concerns by reducing inflammation, oxidative stress, and hyperpigmentation while promoting wound healing. This soluble rutin offers a promising solution for the rapid treatment of maskne-related disorders and other skin problems caused by prolonged mask use.

Long-term results of radiosurgery for cerebral arteriovenous malformations.

BACKGROUND: Stereotactic radiosurgery (SRS) is known to safely result in a high obliteration rate for small and medium sized arteriovenous malformations (AVM). OBJECTIVE: To evaluate the long-term outcome of patients treated with SRS, with special emphasis given to obliteration and toxicity rates. METHODS: We performed a review of 43 cerebral AVM patients, treated from 1998 to 2008 with a single SRS dose ranging from 21-25 Gy. Of these, 37 had a minimal follow-up of one year. Medical files were reviewed to assess patient and AVM characteristics, the SRS treatment, therapy prior to SRS, the obliteration rate and toxicities. Whenever necessary, outcome data was supplemented by telephone interviews with the patient or treating physician. RESULTS: AVM size was ≥3cm in diameter in 21% of patients. Five patients (11.6%) underwent surgery prior to SRS and 31 patients (72.1%) received one or more embolizations prior to SRS. Of the patients followed with angiography ≥1 year post-SRS, 89% (33/37) had a complete obliteration of the nidus, after a median time of 24.7 months post-treatment. Embolization prior to SRS was not predictive of outcome. One patient suffered a non-fatal haemorrhage between treatment and obliteration. The rate of symptomatic radiation-induced radiological changes was 8.1%. CONCLUSION: Our study shows both obliteration and complication rates in the upper limit of those reported in the literature. SRS seems an attractive treatment option for small AVMs. Unlike other reports, the prior use of embolization did not impact negatively on obliteration rates.

A faster and a stronger defense response: one of the key elements in grapevine explaining its lower level of susceptibility to Esca?

Wood diseases like Esca are among the most damaging afflictions in grapevine. The defense mechanisms in this plant-pathogen interaction are not well understood. As some grapevine cultivars have been observed to be less susceptible to Esca than others, understanding the factors involved in this potentially stronger defense response can be of great interest. To lift part of this veil, we elicited Vitis vinifera plants of two cultivars less susceptible to Esca ('Merlot' and 'Carignan') and of one susceptible cultivar ('Cabernet Sauvignon'), and monitored their defense responses at the leaf level. Our model of elicitation consisted in grapevine cuttings absorbing a culture filtrate of one causal agent of Esca, Phaemoniella chlamydospora. This model might reflect the early events occurring in Esca-affected grapevines. The two least susceptible cultivars showed an earlier and stronger defense response than the susceptible one, particularly with regard to induction of the PAL and STS genes, and a higher accumulation of stilbene compounds and some pathogenesis-related proteins.

Development, implementation, and evaluation of the Apollo model of pediatric rehabilitation service delivery.

This article presents the experience of a rehabilitation program that undertook the challenge to reorganize its services to address accessibility issues and improve service quality. The context in which the reorganization process occurred, along with the relevant literature justifying the need for a new service delivery model, and an historical perspective on the planning; implementation; and evaluation phases of the process are described. In the planning phase, the constitution of the working committee, the data collected, and the information found in the literature are presented. Apollo, the new service delivery model, is then described along with each of its components (e.g., community, group, and individual interventions). Actions and lessons learnt during the implementation of each component are presented. We hope by sharing our experiences that we can help others make informed decisions about service reorganization to improve the quality of services provided to children with disabilities, their families, and their communities.

Listening to Cancer Patients' Narratives During Residency: A Pilot Study on a Communication Skills' Workshop Involving Patients-Partners.

The field of cancer care still lacks best practices in communication. Few postgraduate training programs offer formal training to develop such skills. The patient partnership has been used in medical education to increase the sensitivity of the subjective experiences of patients. In our Canadian center, residents and patient-partners participated in an educational workshop on communication focusing on patient's narrative. The aim of this pilot qualitative study was to explore the experiences of participants in the workshop. Using theoretical sampling, we recruited 6 residents and 6 patient-partners. Semi-structured interviews were conducted and transcribed. A thematic analysis was performed. From analysis, 4 themes emerged: (1) lack of communication skills training; (2) barriers to effective communication in cancer care; (3) the empathy of patient-partners towards the communication challenges faced by residents; and (4) the participants' reactions to the workshop. Based on our findings, our communication skills workshop centered on narrative medicine and involving patient-partners appears feasible. Future research could study its pedagogical value and the optimal learning environment required.