Brachytherapy or external beam radiotherapy as a boost in locally advanced cervical cancer: a Gynaecology Study Group in the Italian Association of Radiation and Clinical Oncology (AIRO) review.

This review analyzes the experience and trends in external beam radiotherapy for delivering a boost in locally advanced cervical cancer, identifying whether radiation therapy modalities impact clinical outcomes with the ultimate aim of evaluating alternatives to brachytherapy. Three independent Italian radiation oncologists conducted a literature search on different external beam radiotherapy boost modalities in locally advanced cervical cancer. The search yielded 30 studies. Eight dosimetric studies, evaluating target coverage and dose to organs at risk, and nine clinical investigations, reporting clinical outcomes, were analyzed. Dosimetric studies comparing external beam radiotherapy boost with brachytherapy produced divergent results, while clinical studies were limited by their retrospective nature, heterogeneous doses, radiation schedules, volumes and techniques, diverse follow-up times, and small cohorts of patients. Evidence emerged that high-tech external beam radiotherapy seemed no better than image-guided brachytherapy for delivering a boost in locally advanced cervical cancer. Prospective clinical studies comparing high-tech external beam radiotherapy and image-guided brachytherapy should be encouraged.

Effects of different types of contingent tactile stimulation on crying, smiling, and sleep in newborns: an observational study.

Sleep, the brain and the ability to interact with the environment change a great deal over the first year of life; however, there are no studies on the possible influence of different environmental stimulations on the organization of subsequent sleep-wake cycles in infants. The hypothesis of this study was that greater continuity of contingent tactile stimulation decreases crying behavior, subsequent active sleep (AS) and its fragmentation, and increases smiling behavior and subsequent quiet sleep in newborns. Forty out of the 82 newborns (15- to 30-hr old) of the initial sample satisfied the inclusion criteria and completed the first cycle of sleep during the period between two feedings. The 40 newborns were randomly assigned to four groups after 2' of baseline observation: continuous stimulation (CS, n = 10); discontinuous nonperiodic stimulation (DnPS, n = 10); discontinuous periodic stimulation (DPS, n = 10); absent stimulation (AbS, n = 10). During baseline measurements, there were no significant differences in crying and smiling behaviors between the four groups, while during the subsequent stimulated wake, the CS group compared to the DnPS group showed more smiling (p < .05) and less crying (p < .05), longer poststimulation wake before sleep (p < .01) as well as AS with a lower percentage of grouped-rapid eye movements [grouped REM (GREM); p < .001]. The number of GREM during AS was negatively correlated to the number of smiles (p < .05) and positively to the number of cries (p < .05) of the previous stimulated wake. These findings suggest that, after birth, different continuity levels of contingent tactile stimulations may affect crying and smiling behaviors and the organization of behavioral states. AS could have an important role in processing affective states.

The Effect of Fibrous Reinforcement on the Polycondensation Degree of Slag-Based Alkali Activated Composites.

Alternative cementitious binders, based on industrial side streams, characterized by a low carbon footprint, are profitably proposed to partially replace Portland cement. Among these alternatives, alkali-activated materials have attracted attention as a promising cementitious binder. In this paper, the chemical stability of the matrix, in fiber-reinforced slag-based alkali-activated composites, was studied, in order to assess any possible effect of the presence of the reinforcement on the chemistry of polycondensation. For this purpose, organic fiber, cellulose, and an inorganic fiber, basalt, were chosen, showing a different behavior in the alkaline media that was used to activate the slag fine powders. The novelty of the paper is the study of consolidation by means of chemical measurements, more than from the mechanical point of view. The evaluation of the chemical behavior of the starting slag in NaOH, indeed, was preparatory to the understanding of the consolidation degree in the alkali-activated composites. The reactivity of alkali-activated composites was studied in water (integrity test, normed leaching test, pH and ionic conductivity), and acids (leaching in acetic acid and HCl attack). The presence of fibers does not favor nor hinder the geopolymerization process, even if an increase in the ionic conductivity in samples containing fibers leads to the hypothesis that samples with fibers are less consolidated, or that fiber dissolution contributes to the conductivity values. The amorphous fraction was enriched in silicon after HCl attack, but the structure was not completely dissolved, and the presence of an amorphous phase is confirmed (C-S-H gel). Basalt fibers partly dissolved in the alkaline environment, leading to the formation of a C-N-A-S-H gel surrounding the fibers. In contrast, cellulose fiber remained stable in both acidic and alkaline conditions.

Alkali Activation of Metallurgical Slags: Reactivity, Chemical Behavior, and Environmental Assessment.

Alkali-activated materials (AAMs) represent a promising alternative to conventional building materials and ceramics. Being produced in large amounts as aluminosilicate-rich secondary products, such as slags, they can be utilized for the formulation of AAMs. Slags are partially crystalline metallurgical residues produced during the high temperature separation of metallic and non-metallic materials in the steelmaking processes. In the present study, the electric arc furnace carbon or stainless steel slag (EAF) and secondary metallurgical slag such as ladle furnace basic slag (LS) were used as precursors in an alkali-activation process. EAF slag, with its amorphous fraction of about 56%, presented higher contents of soluble Si and Al species with respect to ladle slag R (35%). However, both are suitable to produce AAM. The leaching behavior shows that all the release values are below the regulation limit. All the bivalent ions (Ba, Cd, Cu, Ni, Pb, and Zn) are well immobilized in a geopolymeric matrix, while amphoteric elements, such as As and Cr, show a slight increase of release with respect to the corresponding slag in alkaline and aqueous environments. In particular, for Sb and As of AAM, release still remains below the regulation limits, while Mo presents an increase of leaching values that slightly exceeds the limit for landfill non-dangerous waste.

A common disease-associated missense mutation in alpha-sarcoglycan fails to cause muscular dystrophy in mice.

Limb-girdle muscular dystrophy type 2D (LGMD2D) is caused by autosomal recessive mutations in the alpha-sarcoglycan gene. An R77C substitution is the most prevalent cause of the disease, leading to disruption of the sarcoglycan-sarcospan complex. To model this common mutation, we generated knock-in mice with an H77C substitution in alpha-sarcoglycan. The floxed neomycin (Neo)-cassette retained at the targeted H77C alpha-sarcoglycan locus caused a loss of alpha-sarcoglycan expression, resulting in muscular dystrophy in homozygotes, whereas Cre-mediated deletion of the floxed Neo-cassette led to recovered H77C alpha-sarcoglycan expression. Contrary to expectations, mice homozygous for the H77C-encoding allele expressed both this mutant alpha-sarcoglycan and the other components of the sarcoglycan-sarcospan complex in striated muscle, and did not develop muscular dystrophy. Accordingly, conditional rescued expression of the H77C protein in striated muscle of the alpha-sarcoglycan-deficient mice prevented the disease. Adding to the case that the behavior of mutant alpha-sarcoglycan is different between humans and mice, mutant human R77C alpha-sarcoglycan restored the expression of the sarcoglycan-sarcospan complex when introduced by adenoviral vector into the skeletal muscle of previously created alpha-sarcoglycan null mice. These findings indicate that the alpha-sarcoglycan with the most frequent missense mutation in LGMD2D is correctly processed, is transported to the sarcolemma, and is fully functional in mouse muscle. Our study presents an unexpected difference in the behavior of a missense-mutated protein in mice versus human patients, and emphasizes the need to understand species-specific protein quality control systems.

Intraluminal Brachytherapy in Unresectable Extrahepatic Biliary Duct Cancer: An Italian Pooled Analysis.

BACKGROUND/AIM: To evaluate the outcome of patients with unresectable extrahepatic cholangiocarcinoma (CC) treated with external-beam radiotherapy (EBRT) and concurrent chemotherapy (CT) with or without intraluminal brachytherapy (ILBT) boost or with definitive ILBT. PATIENTS AND METHODS: A pooled analysis of patients with non-metastatic unresectable CC was performed. They were treated in three different institution with EBRT plus CT with or without an ILBT boost. Some patients received only ILBT with curative dose. RESULTS: Seventy-three patients were included in the analysis. Thirty-nine patients (53%) received EBRT treatment with ILBT boost (18 patients with CT during EBRT), while 28 patients (38%) were treated with EBRT (CT in 26 patients) and 6 patients (8.2%) with definitive ILBT (2 patients with CT). CT was administered including either the use of gemcitabine or 5-fluorouracil. With a median follow-up of 16 month (range=1-94 months), median overall survival (OS) was 16 months. Overall median LC was 16 months and patients who underwent ILBT had a better local control (LC) (p=0.018). CONCLUSION: The role of ILBT in unresectable CC is not yet supported by robust evidence in the literature. However, within this limit, preliminary results seem to suggest an improved local control in patients treated with ILBT, almost comparable to the ones of standard chemo-radiotherapy (CRT).

An innovative gynecological HDR brachytherapy applicator system for treatment delivery and real-time verification.

The multichannel vaginal cylinder (MVC) applicator employed for gynecological high dose rate (HDR) brachytherapy increases dose delivery complexity, and thus makes the treatment more prone to errors. A quality assurance (QA) procedure tracking the source throughout dose delivery can detect dwell position and time errors in the multiple channels of the applicator. A new MVC system with integrated real time in vivo treatment delivery QA has been developed based on diodes embedded on the outer surface of the MVC. It has been pre-calibrated and verified using a non-clinical treatment plan with consecutive test positions and dwell times within each catheter, followed by the delivery of ten clinical plans of adjuvant vaginal cuff brachytherapy following hysterectomy for endometrial cancer. The non-clinical verification showed overall mean dwell position and time discrepancies between the nominal and measured treatment of -0.2 ±â€¯0.5 mm and -0.1 ±â€¯0.1 s (k = 1), respectively. The clinical plans showed mean positional discrepancies of 0.2 ±â€¯0.4 and 0.0 ±â€¯0.8 mm, for the central and peripheral catheters, respectively, and mean dwell time discrepancies of -0.1 ±â€¯0.2 and -0.0 ±â€¯0.1 s for central and peripheral catheters, respectively. The innovative prototype of the MVC system has shown the ability to track the source with sub-mm and sub-second accuracy, and demonstrated potential for its incorporation into the clinical routine.

Limb-girdle muscular dystrophy in the United States.

Limb-girdle muscular dystrophy (LGMD) has been linked to 15 chromosomal loci, 7 autosomal-dominant (LGMD1A to E) and 10 autosomal-recessive (LGMD2A to J). To determine the distribution of subtypes among patients in the United States, 6 medical centers evaluated patients with a referral diagnosis of LGMD. Muscle biopsies provided histopathology and immunodiagnostic testing, and their protein abnormalities along with clinical parameters directed mutation screening. The diagnosis in 23 patients was a disorder other than LGMD. Of the remaining 289 unrelated patients, 266 had muscle biopsies sufficient for complete microscopic evaluation; 121 also underwent Western blotting. From this combined evaluation, the distribution of immunophenotypes is 12% calpainopathy, 18% dysferlinopathy, 15% sarcoglycanopathy, 15% dystroglycanopathy, and 1.5% caveolinopathy. Genotypes distributed among 2 dominant and 7 recessive subtypes have been determined for 83 patients. This study of a large racially and ethnically diverse population of patients with LGMD indicates that establishing a putative subtype is possible more than half the time using available diagnostic testing. An efficient approach to genotypic diagnosis is muscle biopsy immunophenotyping followed by directed mutational analysis. The most common LGMDs in the United States are calpainopathies, dysferlinopathies, sarcoglycanopathies, and dystroglycanopathies.

Newborn preference for a new face vs. a previously seen communicative or motionless face.

Newborn infants prefer to look at a new face compared to a known face (still-face). This effect does not happen with the mother-face. The newborns could be attracted by the mother-face because, unlike the still-face, it confirms an expectation of communication. Fifty newborns were video-recorded. Sixteen of them were recruited in the final sample: nine were exposed to a communicative face and seven to a still-face. All the 16 newborns were successively exposed to two preference-tasks where a new face was compared with the known face. Only newborns previously exposed to a still-face preferred to look at a new face instead of the known face. The results suggest that the newborns are able to build a dynamic representation of faces.