Single fraction of HDR brachytherapy for prostate cancer: Results of the SiFEPI phase II prospective trial.

Purpose: To report the results of the Single Fraction Early Prostate Irradiation (SiFEPI) phase 2 prospective trial. Materials/Methods: The SiFEPI trial (NCT02104362) evaluated a single fraction of high-dose rate brachytherapy (HDB) for low- (LR) and favorable-intermediate (FIR) risk prostate cancers. After rectal spacer placement, a single fraction of 20 Gy was delivered to the prostate. Oncological outcome (biochemical (bRFS) and local (lRFS) relapses, disease-free (DFS) and overall (OS) survivals and toxicity (acute/late genito-urinary (GU), gastro-intestinal (GI) and sexual (S) toxicities were investigated. Results: From 03/2014 to 10/2017, 35 pts were enrolled, of whom 33 were evaluable. With a median age of 66 y [46-79], 25 (76 %) and 8 (24 %) pts were LR and FIR respectively. With a MFU of 72.8 months [64-86], 6y-bRFS, lRFS and mRFS were 62 % [45-85], 61 % [44-85] and 93 % [85-100] respectively while 6y-DFS, CSS and OS were 54 % [37-77], 100 % and 89 % [77-100] respectively. Late GU, GI and S toxicities were observed in 11 pts (33 %;18G1), 4 pts (12 %;4G1) and 7 pts (21 %;1G1,5G2,1G3) respectively. Biochemical relapse (BR) was observed in 11 pts (33 %;7LR,4FIR) with a median time interval between HDB and BR of 51 months [24-69]. Nine of these pts (82 %) presented a histologically proven isolated local recurrence. Conclusions: Long-term results of the SiFEPI trial show that a single fraction of 20 Gy leads to sub-optimal biochemical control for LR/FIR prostate cancers. The late GU and GI toxicity profile is encouraging, leading to consideration of HDB as a safe irradiation technique.

High-dose-rate brachytherapy boost for elderly patients with intermediate to high-risk prostate cancer: 5-year clinical outcome of the PROSTAGE cohort.

Purpose: To analyze the oncological outcome in elderly (>70 years) prostate cancer after high-dose rate brachytherapy (HDB) boost. Materials/methods: In this retrospective study, patients with intermediate (IR) and high-risk (HR) prostate cancer underwent external beam radiation therapy (EBRT) followed by HDB boost with/without androgen deprivation therapy (ADT). The impact of age (≤70y vs. > 70y) was investigated. Oncological outcome focused on biochemical relapse-free survival (bRFS), cause-specific (CSS) and overall survival (OS). Late genito-urinary (GU) and gastro-intestinal (GI) toxicities were investigated. Results: From 07/08 to 01/22, 518 pts received a HDB boost, and 380 were analyzed (≤70y:177pts [46.6%] vs. > 70y:203pts [53.4%]). Regarding NCCN classification, 98 pts (≤70y: 53pts; >70y: 45pts; p = 0.107) and 282 pts (≤70y: 124pts; >70y: 158pts; p = NS) were IR and HR pts respectively. Median EBRT dose was 46 Gy [37.5-46] in 23 fractions [14-25]. HDB boost delivered a single fraction of 14/15 Gy (79%). ADT was used in 302 pts (≤70y: 130pts; >70y: 172pts; p = 0.01). With MFU of 72.6 months [67-83] for the whole cohort, 5-y bRFS, 5-y CSS and 5-y OS were 88% [85-92], 99% [97-100] and 94% [92-97] respectively; there was no statistical difference between the two age groups except for 5-y CSS (p = 0.05). Late GU and GI toxicity rates were 32.4% (G ≥ 3 7.3%) and 10.1% (no G3) respectively. Conclusions: For IR and HR prostate cancers, HDB boost leads to high rates of disease control with few late G ≥ 3 GU/GI toxicities. For elderly pts, HDB boost remains warranted mainly in HR pts, while competing comorbidity factors influence OS.

Combination of Soxhlet extraction and catalytic hydrodebromination for remediation of tetrabromobisphenol A contaminated soil.

As a widely used brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) has been detected in various environmental matrices and is known to cause negative effects on both the environment and human health. In this study, a combined method was developed for the abatement of TBBPA contaminated soil based on successive steps of solvent extraction (SE) and catalytic hydrodebromination (HDB) over Pd/C. The results showed that TBBPA could be efficiently extracted from the TBBPA contaminated soil with polar solvents. Subsequently, TBBPA could be completely hydrodebrominated over Pd/C in ethanol, via multistep ultimately yielding bisphenol A. Moreover, NaOH, NH3H2O, and Et3N were more favorable to promote the HDB of 4-TBBPA over Pd/C, and 100% bromide atom removal ratio of TBBPA was achieved within 40 min when [NaOH]0/[organic-Br]0 was more than 1.10 in ethanol. However, the catalytic activity of Pd/C decreased with the repeated use in ethanol. To study the mechanism for this phenomenon, fresh and used catalysts were analyzed by characterization techniques including scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-ray spectrometer (EDS). It was found that the deactivation of Pd/C catalyst caused by the gradual accumulation of NaBr could be recovered by washing with water. On the basis of these studies, an effective and practical system for the combined method of SE and catalytic HDB over Pd/C was developed to dispose BFRs contaminated soils.

Gut Microbiota-Mediated Immunomodulatory Effects of Lactobacillus rhamnosus HDB1258 Cultured in the Lava Seawater in the Colitis Mouse Model.

The immunomodulatory effects of Lactobacillus rhamnosus HDB1258 were evaluated in mice with colitis induced by Klebsiella oxytoca (KO). L. rhamnosus HDB1258 was cultured in the lava seawater (LS) to improve its probiotic properties. It increased adhesive ability to mucin with mRNA expression levels of chaperone proteins (such as GroEL/ES, DnaKJ, and HtrA). In the in vivo experiments, administration of KO caused an inflammation on the colon with gut dysbiosis. LH group (oral gavage of HDB1258 1.0 × 109 colony forming units/day) showed that inflammatory biomarkers, including IL-1ß, TNF-α, IL-6, and PGE2, were significantly decreased to less than half of the KO group, and Th1 cells were decreased in the spleen, but Treg cells were not affected. In contrast, the expression levels of secretory IgA and IL-10 were significantly increased, and the composition of gut microbiota in the LH group tended to recover similar to normal mice without any effect on the α-diversity. In conclusion, L. rhamnosus HDB1258 cultured in the LS could regulate competitively pathogenic bacteria in imbalanced flora with its improved mucin adhesive ability and was an effective immunomodulatory adjuvant for treating colitis by its regulatory function on intestinal inflammation.

Lactobacillus rhamnosus HDB1258 modulates gut microbiota-mediated immune response in mice with or without lipopolysaccharide-induced systemic inflammation.

BACKGROUND: Gut microbiota closely communicate in the immune system to maintain a balanced immune homeostasis in the gastrointestinal tract of the host. Oral administration of probiotics modulates gut microbiota composition. In the present study, we isolated Lactobacillus rhamnosus HDB1258, which induced tumor necrosis factor (TNF)-α and interleukin (IL)-10 expression in macrophages, from the feces of breastfeeding infants and examined how HDB1258 could regulate the homeostatic immune response in mice with or without lipopolysaccharide (LPS)-induced systemic inflammation. RESULTS: Oral administration of HDB1258 significantly increased splenic NK cell cytotoxicity, peritoneal macrophage phagocytosis, splenic and colonic TNF-α expression, TNF-α to IL-10 expression ratio, and fecal IgA level in control mice, while Th1 and Treg cell differentiation was not affected in the spleen. However, HDB1258 treatment significantly suppressed peritoneal macrophage phagocytosis and blood prostaglandin E2 level in mice with LPS-induced systemic inflammation. Its treatment increased LPS-suppressed ratios of Treg to Th1 cell population, Foxp3 to T-bet expression, and IL-10 to TNF-α expression. Oral administration of HDB1258 significantly decreased LPS-induced colon shortening, myeloperoxidase activity and NF-κB+/CD11c+ cell population in the colon, while the ratio of IL-10 to TNF-α expression increased. Moreover, HDB1258 treatment shifted gut microbiota composition in mice with and without LPS-induced systemic inflammation: it increased the Cyanobacteria and PAC000664_g (belonging to Bacteroidetes) populations and reduced Deferribacteres and EU622763_s group (belonging to Bacteroidetes) populations. In particular, PAC001066_g and PAC001072_s populations were negatively correlated with the ratio of IL-10 to TNF-α expression in the colon, while the PAC001070_s group population was positively correlated. CONCLUSIONS: Oral administered HDB1258 may enhance the immune response by activating innate immunity including to macrophage phagocytosis and NK cell cytotoxicity in the healthy host and suppress systemic inflammation in the host with inflammation by the modulation of gut microbiota and IL-10 to TNF-α expression ratio in immune cells.

Endocrine therapy with accelerated Partial breast irradiatiOn or exclusive ultra-accelerated Partial breast irradiation for women aged ≥ 60 years with Early-stage breast cancer (EPOPE): The rationale for a GEC-ESTRO randomized phase III-controlled trial.

PURPOSE: Breast cancer in the elderly has become a public health concern; there is a need to re-design its treatment with a view to de-escalation. Our paper sets out the rationale for a phase 3 randomized trial to evaluate less burdensome adjuvant procedures that remain effective and efficient. MATERIALS AND METHODS: For low-risk breast cancer in the elderly, adjuvant treatment has been adjusted in order to make it more suitable and efficient. Hypofractionated radiation therapy based on accelerated or non-accelerated regimens as well as accelerated and ultra-accelerated partial breast irradiation (APBI) protocols were reviewed. Withdrawal of radiation (RT) or endocrine therapies (ET) from the adjuvant procedure were also investigated. Based on molecular and APBI classifications, inclusion criteria were discussed. RESULTS: Phase 3 randomized trials which compared standard vs. accelerated/non-accelerated hypofractionated regimens confirmed that the latter were non-inferior in terms of local control. Similarly, except for intraoperative-based techniques, APBI achieved non-inferior local control rates compared to whole breast irradiation for low-risk breast cancer. In phase 2 prospective trials using ultra APBI, encouraging results were observed regarding oncological outcome and toxicity profile. In phase 3 trials, adjuvant ET without RT significantly increased the rate of local relapse with no impact on overall survival while RT alone proved effective. Elderly patients aged 60 or more with low-risk, luminal A breast cancer were chosen as the target population in a phase 3 randomized trial comparing APBI + 5-year ET vs. uAPBI (16 Gy 1f) alone. CONCLUSION: To investigate de-escalation adjuvant treatment for elderly breast cancer patients, we have defined a road map for testing more convenient strategies. This EPOPE phase 3 randomized trial is supported by the GEC-ESTRO breast cancer working group.

High-dose rate brachytherapy in localized penile cancer: 5-Year clinical outcome analysis.

PURPOSE: To analyze the oncological outcome and toxicity profile after conservative treatment based on multicatheter interstitial high-dose rate brachytherapy (MHB) for patients presenting a localized penile cancer. MATERIALS AND METHODS: Patients with histologically proven, non-metastatic (T1-T2 N0-N2 M0) localized penile cancer were treated with MHB. Needles were placed under general anesthesia into the target volume using a dedicated template. Treatment planning was performed using a post-implant CT-scan to deliver 35 Gy or 39 Gy (9f, 5d) for adjuvant or definitive treatment respectively. Five-year oncological outcome was evaluated with local relapse-free (LRFS), regional relapse-free (RRFS), and metastasis-free survival (MFS), specific (SS) and overall survival (OS). In pre-treatment and follow-up consultations, skin, urinary and sexual toxicities were investigated using CTCAEv4.0 classification, International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5-items (IIEF-5). Dosimetry data were also analyzed. RESULTS: From 03/2006 to 05/2020, with a median follow-up of 72.4 months [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], 29 pts, mainly T1 (75.9%) and N0 (89.7%), underwent MHB. Eleven (38%) and 18 pts (62%) received MHB as adjuvant or definitive treatment respectively. Five-year LRFS, RRFS, MFS, SS and OS were 82%, 82%, 89%, 88% and 73% respectively. Six patients (20.7%) experienced local relapse and underwent salvage penectomy leading to a penile preservation rate of 79.3%. Acute skin toxicity was reported 1 month after MHB, with 28% G1, 66% G2 and 6% G3. Late skin complications were telangiectasia for 5 pts (17%) and necrosis for 3 pts (10.3% requiring hyperbaric oxygen therapy). Comparing pre- and post-treatment status, no significant change was observed for skin appearance, IPSS and IIEF-5. CONCLUSION: MHB represents an efficient first line conservative treatment option for early penile cancers. Oncological outcome and late toxicity profile appear encouraging. However, larger-scale cohorts with longer follow-up are needed to more accurately precise the features of the best candidate to MHB.

Recent developments in biomaterials for long-bone segmental defect reconstruction: A narrative overview.

Reconstruction of long-bone segmental defects (LBSDs) has been one of the biggest challenges in orthopaedics. Biomaterials for the reconstruction are required to be strong, osteoinductive, osteoconductive, and allowing for fast angiogenesis, without causing any immune rejection or disease transmission. There are four main types of biomaterials including autograft, allograft, artificial material, and tissue-engineered bone. Remarkable progress has been made in LBSD reconstruction biomaterials in the last ten years. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our aim is to summarize recent developments in the divided four biomaterials utilized in the LBSD reconstruction to provide the clinicians with new information and comprehension from the biomaterial point of view.

La mutualidad perlocutiva en la comunicación preverbal en niños con madres con depresión postparto / Perlocutive mutuality in preverbal communication in children with mothers with postpartum depression

Esta revisión bibliográfica es un estudio teórico que presenta avances, actualización, comparación y análisis crítico de los resultados obtenidos en trabajos empíricos de autores nacionales e internacionales del campo de la Psicolingüística y referidos puntualmente al desarrollo infantil (Montero & León, 2007). Se hace hincapié en las cualidades de las interacciones madre-hijo en la etapa pre-lingüística, en situaciones de ausencia y presencia de indicadores de patología mental materna (específicamente depresión postparto- DPP). Se describe una serie de patrones y modalidades de comunicación que mamá y bebé adoptan durante dicha fase del desarrollo del lenguaje. En primer término, se presenta la caracterización acústica y kinestésica que el Habla Dirigida al Bebé (HDB) adquiere durante la etapa preverbal, diferenciando entre los patrones comunicacionales que corresponden tanto a los mensajes emitidos como recibidos y en segundo lugar, la caracterización acústica y kinésica de los patrones comunicacionales infantiles durante la primera etapa del desarrollo del lenguaje. Posteriormente, se plantea cómo resultan afectados dichos patrones en madres con indicios de DPP, identificando los patrones de comunicación del HDB en madres -con y sin DPP-, tanto los referidos a la emisión (aspectos acústicos, discursivos y kinestésicos) como a la recepción (aspectos perceptuales), así cómo se ven afectados los patrones comunicativos en los bebés de madres con DPP. Por último, se concluye sobre la trascendencia que tiene conocer las desviaciones observables en el proceso comunicativo mamá-bebé para el trabajo terapéutico en el vínculo diádico y para el desarrollo integral del infante.

This article is a theoretical review that analyzes the results of various psycholinguistic researches on language acquisition during the prelinguistic stage depending on the mother-child relationship in situations of absence and presence of mind pathology indicators-specifically maternal postpartum depression (PPD). It follows the description of a series of patterns and modes of communication that mother and son take during this phase of language development, following the findings of national and international renowned authors dedicated to this subject. This paper seeks, in the first instance, to conceptualize and establish the main properties of communicative exchanges that occur in the mother-child interactions during the preverbal stage in situations of no obvious pathology in the mother or the infant. Secondly, sought to focus on how these patterns and / or modes of interaction are affected when the mother shows signs of emotional involvement, timely postpartum depression. And also how, therefore, this affects these communicative exchanges. Indeed, this study will present a literature review of existing research data on the effects on the communication patterns between mother and baby-during preverbal stage- when the mother suffers PPD. This improvement is important because so far these data have not been found on one paper -but compiled partially written in various research- nor presented discriminating patterns that the various modes of communication that are acquired and used by each member of the dyad. Regarding the first objective, the results have been made by several scientific papers related to the characteristics that each of the modes in which communication between the preverbal child and primary adult caretaker-usually the mother- occurs. From this, one could envision that prosody is the feature of the HDB that has been studied through the objective measurement of various acoustic aspects such as fundamental frequency, melodic contours and pitch ranges. The combination, features and ways of using the various modes of communication depend intrinsically on the relationships between the biological, psychological, social and contextual conditions that occur and determine the course and the qualities of the mother-infant interaction. Regarding the second objective, it was possible to envision that when the mother is not emotionally available to the baby's demands behavior of the pair may be asynchronous. Even children of mother with PPD may get to use self-regulatory behaviors such as gaze aversion in order to reduce the negative affect arising from the lack of responsiveness and withdrawal that characterize the behavioral repertoire of their mothers (Tronick & Gianino, 1986). However, a substantial stand out in terms of the information gathered at this point of theoretical review, it was found that most of the data and reported results derived from research in developed European countries (mainly Germany and England) and United State. And samples were made up of middle-class mothers and / or high average, with a minimum level of higher education at age 13, adults, gilts or just another child without complications in pregnancy and childbirth and with healthy term infants. Just one research formed a heterogeneous sample of mothers from different races, belonging to lower social strata and lower education level -Kaplan, Burgess, Sliter, & Moreno, 2009). This implies that this investigation results can be generalized to the type of population, culture, language and race that has been studied. In the section dedicated to discussing matters relating to the socio-demographic characteristics of the sample and biases found, make impossible to universalize the results of detailed research group here treated. Finally, it concludes on the importance of knowing the observable deviations in the communication process mom-baby has for therapeutic work on the dyadic relationship, in general, and for the development of the infant, particularly.

Systemic administration and local microinjection into the central nervous system of the 5-HT(7) receptor agonist LP-211 modify the sleep-wake cycle in the rat.

The effects of LP-211, a selective serotonin 5-HT7 receptor agonist were studied in adult rats implanted for chronic sleep recordings. Intraperitoneal administration of LP-211 (2.5-10mg/kg) during the light phase of the light-dark cycle significantly increased wakefulness (W) and reduced rapid-eye-movement sleep (REMS) and the number of REM periods during the 6-h recording period. Direct infusion of LP-211 into the dorsal raphe nucleus (DRN) (2-6 mM), locus coeruleus nucleus (LC) (4 mM), basal forebrain (horizontal limb of the diagonal band of Broca) (HDB) (2 mM) or laterodorsal tegmental nucleus (LDT) (4 mM) induced also a decrease of REMS. Additionally, microinjection of the 5-HT7 receptor ligand into the HDB (2 mM) augmented W. Presently, there is no satisfactory explanation for the effect of 5-HT7 receptor activation on W and REMS occurrence. Additional studies are required to characterize the neurotransmitter systems responsible for the actions of LP-211 on the behavioral states.

THE EXPRESSION OF TrkA AND ChAT IN NEURONS OF THE HORIZONTAL LIMB OF DIAGONAL BAND OF DIFFERENTLY AGED RATS──AN IMMUNOHISTOCHEMICAL STUDY / 解剖学报

Objective To investigate the postnatal developmental rule of TrkA and ChAT\|immunoreactive(ChAT\|ir) neurons and the relationship between TrkA and ChAT\|ir neurons in the horizontal limb of diagonal band(HDB) of rats. Methods Immunohistochemistry technique combined with image analyser were used. Results TrkA and ChAT\|ir neurons localized in the neurons of basal forebrain of rats. TrkA immunostaining was present at postnatal day 1(PD1), but ChAT immunostaining was present at PD5 Most densely stained TrkA and ChAT neuronal bodies and fibers were present at PD20, while the mean grey degrees of TrkA and ChAT\|ir neurons reached to the peak. Both TrkA and ChAT began to decline at PD30 and maintain a relatively higher level in the adult. However, during aging both TrkA and ChAT\|ir neurons atrophied and became smaller than that of adult. The number of TrkA and ChAT\|ir neurons decreased 39 8% and 33 3%;the mean areas 15 7% and 12 8%; the mean grey degree values were 29 9% and 9 9%, respectively. The mean areas, grey degrees and numbers of TrkA and ChAT\|ir neurons from PD5 to aged rats had positive correlation. Conclusion The results indicate that the expression of TrkA was earlier than ChAT. The expression of TrkA and ChAT followed a very similar temporal pattern in HDB from PD5 to aged rats, suggesting that TrkA may participate in the regulation of ChAT\|ir neuronal development, differentiation, maturation and aging. The down\|regulation of TrkA and ChAT of aged rats is associated with neuronal atrophy and loss and may contribute to the pronounced vulnerability of these neurons to degeneration in aging animals and Alzheimer disease.\;