The aim of this Phase II, non-randomized study was to assess activity and safety of neoadjuvant chemotherapy (NACT) before chemoradiation (CT/RT) followed by radical surgery (RS) in locally advanced ...cervical cancer (LACC) patients.
The primary end point was rate of pathologic complete response (pCR). FIGO Stage IB2-IVA patients were administered NACT chemotherapy (paclitaxel 80 mg/m2, carboplatin AUC 2), for 6 weeks, followed by Intensity Modulated Radiotherapy plus simultaneous boost (total dose of 50.4 Gy to CTV1, and 39.6 Gy to CTV2). Clinical response was assessed according to RECIST criteria. Responsive patients were triaged to RS. The regimen would be considered active if >20 pCRs were registered in 39 patients.
45 patients were enrolled into the study; 25 patients (55.5%) were FIGO stage IIB, 9 cases (20.0%) had stage III disease. At work up, pelvic lymph node involvement was documented in 38 (84.4%) patients; pCR was documented in 18 out of 40 patients (45.0%). Grade 3–4 hematological toxicity after NACT occurred in 4 patients; CT/RT associated grade 3 toxicity was found in 7 patients. Early and late postoperative complications were detected in 16, and 11 cases, respectively. Three-year PFS and OS were 66.0% and 86.0%, respectively.
NACT followed by CT/RT by IMRT and RS, is feasible and safe; failure to achieve the primary endpoint has to be recognized; however, enrollment of a higher rate of poor prognosis patients compared to historical data used to calculate sample size, could have resulted in reduced activity.
Aim
Orthorexia nervosa (ON) is a condition characterized by an excessive importance attributed to the intake of healthy foods. This study was aimed at investigating the prevalence of ON in subjects ...with type 1 diabetes (T1D) compared to control subjects.
Methods
Patient with T1D using either flash glucose monitoring or continuous glucose monitoring were enrolled. For the selection of control group, each patient was asked to indicate one non-diabetic subject of their same sex and approximate age among colleagues at work and school. Patients and controls completed the following questionnaires: ORTO-15, Dusseldorf Orthorexie Scale (DOS), Eating Disorder Examination Questionnaire (EDE-Q) and Brief Symptom Inventory (BSI). The principal outcome was the prevalence of ON among T1D and control subjects.
Results
We enrolled 44 patients with T1D aged 39.7 ± 15.7 years, with BMI 24.3 ± 4.3 kg/m
2
, and mean HbA1c 53.5 49–57 mmol/mol. Control subjects were similar to T1D with respect to sex, age and BMI. Thirty-two 72% and 29 65% subjects among patients and controls, respectively, had ORTO15 < 40 (between-group
p
= 0.48). Two (4.5%) and zero subjects among patients and controls, respectively, had DOS ≥ 30 (
p
= 0.29). Median scores of DOS, but not of ORTO-15, were significantly higher in patients than in controls. None of the metabolic variables showed a correlation with psychometric tests in T1D.
Conclusion
Although the prevalence of ON was not significantly higher in T1D than in controls, patients with T1D showed higher scores of some, but not all, tests assessing orthorexia, without any significant correlation with metabolic parameters.
Aging is marked by a progressive rise in chronic diseases with an impact on social and healthcare costs. Physical activity (PA) may soothe the inconveniences related to chronic diseases, has positive ...effects on the quality of life and biological rhythms, and can prevent the decline in motor functions and the consequent falls, which are associated with early death and disability in older adults.
We randomized 120 over-65 males and females into groups of similar size and timing and will give each either moderate physical activity or cultural and recreational activities. Being younger than 65 years, inability to participate in physical activity for any medical reason, and involvement in a massive program of physical exercise are the exclusion criteria. The primary outcome measures are: quality of life, walking speed, and postural sway. Participants are tested at baseline, post-treatment, and 6-month (24 weeks) and 12-month (48 weeks) follow-ups.
This study aims at improving the quality of life, wellness, and cognitive functioning in the elderly through a low-cost affordable program of moderate physical activity. Given the growing aging of the world population and the social and economic burden of disability in the elderly, our results might have a major impact on future practices.
ClinicalTrials.gov NCT03858114 . Registered on 28 February 2019.
Analysis of single-molecule brightness allows subunit counting of high-order oligomeric biomolecular complexes. Although the theory behind the method has been extensively assessed, systematic ...analysis of the experimental conditions required to accurately quantify the stoichiometry of biological complexes remains challenging. In this work, we develop a high-throughput, automated computational pipeline for single-molecule brightness analysis that requires minimal human input. We use this strategy to systematically quantify the accuracy of counting under a wide range of experimental conditions in simulated ground-truth data and then validate its use on experimentally obtained data. Our approach defines a set of conditions under which subunit counting by brightness analysis is designed to work optimally and helps in establishing the experimental limits in quantifying the number of subunits in a complex of interest. Finally, we combine these features into a powerful, yet simple, software that can be easily used for the analysis of the stoichiometry of such complexes.
As part of the discipline and practice of design (understood in its broadest sense of «strategic problem-solving process that drives innovation, builds business success, and leads to a better quality ...of life through innovative products, systems, services, and experiences» ICSID, 2015), the conflict has always had a fundamental role as evolutionary impulse of genuine cultural regeneration that is expressed through the visions of artifacts, whether physical or cognitive, their meanings, their roles, practices and relationships, the imaginaries that they create or are associated with. Artifacts give voice, in their forms and in their behavior, to social and collective conflicts between worlds and between representations – Internal / external, past / present, tradition / innovation, individuality / standardization – and their pervasiveness, narrative force and creation of experiences, present themselves as messengers and interpreters at the same time, of dissensions and conflicts of contemporaneity. The speculative attitude of critical design, in example «uses speculative design proposals to challenge narrow assumptions, preconceptions and givens about the role products play in everyday life» (Dunne, Raby, 2013, p. 34): with their projects Anthony Dunne and Fiona Raby challenge the power of consumerism, the brands and the use of pre-established objects; similarly fiction design (Sterling, 2005; Bleecker, 2009) represents and investigates dystopian worlds «in order to create a discursive space, where 'something' may mean 'anything'» (Lindley, Coulton, 2015, pp. 210-211). This translates concretely into “provocative” design forms, such as that of the Near Future Laboratory which offers a catalog of fictional objects, ie extra-ordinary prototypes that could be part of the normal daily life of the near future. The same visionary attitude, combined with the envisioning capacity of design, is rather typical of the DesignArt (Coles, 2005; Lupo, 2011) where technological, symbolic and relational aesthetic straddling art and design combine to generate artifacts according to a logic of disruptive innovation and a critical-conceptual attitude exemplified also by the exhibition “disobedient objects” (by designer Giulio Iachetti, held in Milan Triennale, 2008) «who rebel against the logic of consumption, sow doubts and who aspire to be something else». (Iacchetti, 2009). The essay aims to define, explore, critically and phenomenologically, the phenomenon of dissenting design as an act not simply oriented towards solutions and needs, but establishing conversation devices for an ongoing social, political and cultural commitment.
Serum thyrotropin (TSH) receptor antibodies (TRAbs) are occasionally found in patients with amiodarone-induced thyrotoxicosis (AIT), and usually point to a diagnosis of type 1 AIT (AIT1) due to ...Graves' disease (GD). However, the TRAb role and function in AIT have not been clarified.
A retrospective cohort study of 309 AIT patients followed at a single academic center over a 30-year period. AIT TRAb-positive patients (
= 21, 7% of all cases) constituted the study group; control groups consisted of type 2 AIT (AIT2) TRAb-negative patients (
= 233), and 100 non-AIT patients with GD. Clinical and biochemical data at diagnosis and during the course of disease were compared. Histological samples of patients who had total thyroidectomy were reviewed. Stored serum samples were used for a functional assay of TRAb class G immunoglobulins (IgGs) in Chinese hamster ovary (CHO) cells stably transfected with complementary DNA encoding for the TSH receptor.
TRAb-positive patients were grouped according to color flow Doppler sonography, radioactive iodine thyroid uptake, and duration of amiodarone therapy before thyrotoxicosis in type 1 (
= 9, 43%; TRAb1) or type 2 (
= 12, 57%; TRAb2) AIT. TRAb1 patients had clinical and biochemical features indistinguishable from GD controls, and were responsive to methimazole. Conversely, TRAb2 patients had clinical features similar to AIT2 controls, and were responsive to glucocorticoids, but not to methimazole. The CHO cell functional assay demonstrated that TRAb1 IgGs had a stimulatory effect on cyclic AMP production, which was absent in TRAb2 IgGs. Pathology in TRAb1 showed hyperplastic thyroid follicles and mild lymphocyte infiltration, reflecting thyroid stimulation. On the contrary, TRAb2 samples revealed follicle destruction, macrophage infiltration, and sometimes fibrosis, consistent with a destructive process.
Almost 60% of TRAb-positive AIT patients had a destructive thyroiditis. TRAb-positive tests in AIT patients do thus not necessarily imply a diagnosis of GD and AIT1, and should be evaluated in the clinical and biochemical setting of each AIT patient and confirmed by measuring thyroid-stimulating immunoglobulins.
Amphiphilic maleic acid-containing polymers allow for the direct extraction of membrane proteins into stable, homogenous, water-soluble copolymer/lipid nanoparticles without the use of detergents. By ...adjusting the polymer/lipid ratio, the size of the nanoparticles can be tuned at convenience for the incorporation of protein complexes of different size. However, an increase in the size of the lipid nanoparticles may correlate with increased sample heterogeneity, thus hampering their application to spectroscopic and structural techniques where highly homogeneous samples are desirable. In addition, size homogeneity can be affected by low liposome solubilization efficiency by DIBMA, which carries a negative charge, in the presence of high lipid charge density.
In this work, we apply biophysical tools to characterize the size and size heterogeneity of large (above 15 nm) lipid nanoparticles encased by the diisobutylene/maleic acid (DIBMA) copolymer at different DIBMA/lipid ratios and percentages of anionic lipids. Importantly, for nanoparticle preparations in the diameter range of 40 nm or below, the size homogeneity of the DIBMA/lipid nanoparticles (DIBMALPs) remains unchanged. In addition, we show that anionic lipids do not affect the production, size and size homogeneity of DIBMALPs. Furthermore, they do not affect the overall lipid dynamics in the membrane, and preserve the functionality of an enclosed membrane protein.
This work strengthens the suitability of DIBMALPs as universal, native-like lipid environments for functional studies of membrane proteins and provide useful insight on the suitability of these systems for those structural techniques requiring highly homogeneous sample preparations.
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•Size heterogeneity of DIBMALPs is not dependent on DIBMALPs size (below 40 nm).•DIBMALPs result quite heterogeneous in particle size compared to SMALPs.•Variable amounts of anionic lipids do not affect DIBMALPs size and homogeneity.•Anionic lipids in DIBMALPs do not affect lipid dynamics and protein functionality.•This study provides insights on DIBMALPs size heterogeneity for structural studies.
Julius Robert von Mayer was among the first to state the principle of energy conservation. As a medical doctor, he was interested in the relationship between heat and work, being stimulated by ...observations and considerations regarding the physiology of the human body. In 1842, he published a first manuscript in which he reported the value of the mechanical equivalent of heat; then, in a paper in 1845, he elucidated the procedure followed for the calculation of the equivalent. The result achieved by Mayer, based only on theoretical calculations, was presented before the experimentally determined value obtained by Joule in 1847 and remains of capital interest in the history of thermodynamics.
Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment.
This Randomized Controlled Trial (RCT) was set up to verify ...whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance.
RCT with parallel and balanced large groups.
Academic university hospital and Olympic gyms.
People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity.
Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of "life movements", strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales.
At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046).
A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes.
: NCT03858114.
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