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Eric Dupont,1 Michel Journet,2 Marie-Laure Oula,3 Juan Gomez,1 Claude Léveillé,4 Estelle Loing,5 Diane Bilodeau6 1Immanence IDC Inc, Québec, QC, Canada; 2Clinique de Dermatologie St-Joseph, Montréal, QC, Canada; 3Evalulab Inc, Mont-Royal, QC, Canada; 4Clinique de Chirurgie Esthétique du Québec Métropolitain, Lévis, QC, Canada; 5Lucas Meyer Cosmetics, Québec, QC, Canada; 6CosmeConsult, Québec, QC, Canada Background: Cellulite is a serious cosmetic concern for most of the 90% of women affected by it. Objective: To assess the clinical efficacy of a complex integral anti-cellulite gel. Methods: This double-blind, randomized, placebo-controlled study involved 44 healthy women, aged 25–55 years. Subjects had a normal to slightly overweight body mass index and presented slight to moderate cellulite on their thighs, buttocks, and/or hips at baseline. Subjects were randomly assigned to either the treated or placebo group and accordingly applied the active product or placebo on their hips, stomach, buttocks, and thighs, twice daily for 3 months. Skin tonicity, orange-peel aspect, and stubborn cellulite were assessed at day 0, 28, 56, and 84. A self-evaluation questionnaire was completed by all volunteers. Results: At the end of the study, an average of 81% of the subjects applying the active product presented improvement in their cellulite condition versus 32% for the placebo group (all descriptors and sites combined). At day 84, skin tonicity, orange-peel appearance, and stubborn cellulite were improved in a significant manner (P

Messenger RNAs (mRNAs) in higher eukaryotes that encode proteins important for the assembly of the translational apparatus (e.g., ribosomal proteins) often harbor a pyrimidine-rich motif at the extreme 5' end known as a 5' terminal oligopyrimidine (5'TOP) sequence. Members of the La-related protein 1 (LARP1) family control 5'TOP expression through a conserved DM15 motif, but the mechanism is not well understood. 5'TOP motifs have not been described in many lower organisms, and fission yeast harbors a LARP1 homolog that also lacks a DM15 motif. In this work, we show that the fission yeast LARP1 homolog, Slr1p, controls the translation and stability of mRNAs encoding proteins analogous to 5'TOP mRNAs in higher eukaryotes, which we thus refer to as proto-5'TOPs. Our data suggest that the LARP1 DM15 motif and the mRNA 5'TOP motif may be features that were scaffolded over a more fundamental mechanism of LARP1-associated control of gene expression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Clinical evidence has suggested that the oat-soluble fiber β-glucan might have lipid-lowering effects., Objectives: The present clinical trial was conducted to evaluate the efficacy and safety of high-medium molecular weight β-glucan on serum low-density lipoprotein (LDL) cholesterol and other lipid subfractions in subjects with hyperlipidemia., Methods: A randomized double-blinded trial was performed to assess the efficacy and safety of β-glucan supplementation in reducing lipid levels. Subjects with LDL cholesterol levels of >3.37 mmol/L when treated or not with a statin were randomly assigned to receive 1 of 3 daily doses of a tableted formulation of β-glucan (1.5, 3, or 6 g) or placebo. The primary efficacy end point was the change from baseline to 12 wk in LDL cholesterol. Secondary end points of lipid subfractions and safety were also assessed., Results: A total of 263 subjects were enrolled; 66 subjects were assigned to each of the 3 β-glucan groups, and 65 subjects were assigned to the placebo group. The mean change from baseline to 12 wk in serum LDL cholesterol level was 0.08, 0.11, and -0.04 mmol/L in the 3 β-glucan groups (P = 0.23, 0.18, and 0.72 compared with the placebo group, respectively) and -0.10 mmol/L in the placebo group. The changes in total cholesterol, small LDL cholesterol subclass particle concentration, non-high-density lipoprotein cholesterol, apolipoprotein B, very low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein were also not significant in the β-glucan groups when compared with the placebo group. Gastrointestinal adverse events were reported in 23.4%, 34.8%, and 66.7% of patients in the β-glucan groups and in 36.9% of patients in the placebo group (P < 0.0001 for the overall comparison across the 4 groups)., Conclusions: In subjects with LDL cholesterol levels of >3.37 mmol/L, a tablet formulation of β-glucan was not effective in reducing LDL cholesterol concentration or other lipid subfractions when compared with a placebo. This trial was registered at clinicaltrials.gov as NCT03857256., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Most individuals with brain tumours experience distress or cognitive impairment during the illness trajectory, potentially causing decreased quality of life, strain on interpersonal relationships and altered sense of self or of the world. Symptoms of brain tumour and treatment can cause increased reliance on others and decreased in sense of dignity. Dignity is an important consideration when caring for patients, as it can influence decisions at end-of-life. Dignity therapy (DT) is a therapeutic intervention that was developed for patients near the end of life. DT encourages the patient to reflect on the life lived, including important roles and sources of pride, resulting in the development of a 'Legacy Document'. DT has been shown to enhance quality of life and dignity, and reduce psychological and existential distress for patients at the end-of-life. There is little literature on the effectiveness of DT, or other quality of life interventions, in brain tumour populations; This paper reports on the feasibility of conducting DT with this population, and presents qualitative data gathered from patients with brain tumours who participated in DT, their caregivers, and their Dignity Therapists., Methods: Participants were recruited from the Odette Cancer Centre in Toronto. One of five Dignity Therapists conducted the intervention; time data was logged. Immediately after the intervention, patient participants, their caregivers, and Dignity Therapists were sent an open-ended, self-report survey about their experience with DT. Qualitative content analysis was conducted by an impartial reviewer. Average time taken to conduct the intervention was determined., Results: Fifteen out of the 17 recruited participants (88%) completed the intervention; 2 were unable to complete the intervention due to progressing disease. Qualitative data was categorized according to two main areas of interest: Acceptability and Impact. Four participants, 5 caregivers and 4 care providers completed the qualitative surveys. All 4 patient participants reported benefits of DT that related to communication and/or advanced care planning (ACP). Dignity therapists felt that the impact on their patients was positive, and reported satisfaction as a clinician., Conclusions: The low attrition rate for the intervention suggests that DT is feasible in this population, though the required time to complete DT might be difficult for healthcare practitioners to provide within the recommended timeframe for this therapy. Positive qualitative reports on the effect of DT from patients, caregivers and dignity therapists alike indicate that DT is a promising intervention for this demographic.

Background: Elderly glioblastoma (GB) patients are at risk of hospitalizations due to the morbidity of the disease and possible treatment toxicity., Methods: In this observational cohort study, 255 newly diagnosed GB patients age 65 years and older were included. Survival, emergency room visits and admissions to an acute care hospital were determined. Mean and median total health care costs were calculated. Risk factors for Emergency room visits and acute care hospital admissions were determined., Results: Median overall survival was 6 months. The majority of patients (68%) had at least one visit to the emergency department and 77% had at least one admission to acute care. The mean and median total costs (hospital, ambulatory, physician billing, other health care costs) per patient were $162,479.78 (CAN) and $125,511.00 (CAN), respectively. Treatment with radiation or treatment with radio-chemotherapy was associated with a relative risk (RR) of 2.31 (95% CI: 1.44-3.7; P=0.0005) and 2.19 (95% CI: 1.28-3.74; P=0.004), respectively for emergency department visits as compared to patients who were managed with comfort measures only. Patients with a baseline ECOG 0 had a RR of 1.71 (95% CI: 1.06-2.77; P=0.0289) and patients with baseline ECOG 1 had a RR of 1.49 (0.98-2.26; P=0.0623) for hospital admission as compared to patients with ECOG 4., Conclusions: A large proportion of elderly GB patients (particularly those with good baseline performance status who underwent active treatment) presented to the emergency department and had at least one admission to acute care.

Background: Skin redness is a common cosmetic concern affecting predominantly fair-skin individuals and often leading to rosacea. On the basis of the current scientific knowledge of the physiological mechanisms underlying the problem, a complex and integral skin care serum (100RXED2025) was developed and tested clinically for efficacy., Method: Forty-five healthy men and women volunteers, age 30-65, were recruited. All subjects had fair skin (phototype I, II, or III) and presented some degree of skin redness with telangiectasia on the cheeks, the nose, or the nose sides, at baseline. In the course of this open label study, subjects applied the test product on their face, twice daily for 56 days. For each subject, skin redness was evaluated through colorimetric and visual analysis of photographs taken under cross-polarized light at T = 28 (week 4) and T = 56 (week 8), then compared to baseline measurements obtained at day 0., Results: Forty-four volunteers completed the study. On visual evaluation, skin redness had decreased in average by 32.2% at T = 28 (P < 0.001) and by 48.0% at T = 56 (P < 0.001). Importantly, 91% of the subjects showed improvement of skin redness at T = 28, reaching 100% at T = 56. Colorimetric analysis gave an average reduction in redness of 11.6% at T = 28 (P < 0.001) and 13.7% at T = 56 (P < 0.001)., Conclusion: The anti-redness efficacy of the test product was demonstrated after 28 days with further increase following 56 days of application., (© 2012 Wiley Periodicals, Inc.)

Background: Caring for a loved one with a malignant glioma can be a formidable responsibility. The guarded prognosis, side effects of treatments, and changes in brain function, personality and behaviour pose unique challenges in care provision by family members. It is rare that institutions provide educational programs for caregivers., Purpose: To evaluate the impact of providing information in an educational program to caregivers of patients diagnosed with a malignant glioma., Methods: A structured educational program for caregivers of brain tumour patients was developed based upon multidisciplinary expert opinion and caregiver feedback. Twenty-four caregiver participants were enrolled in the program. Knowledge was assessed before, immediately following, and four to six weeks following the program. Open-ended questions were used to explore the caregivers' experiences, as well as additional benefits derived from the program., Results: Knowledge scores on testing immediately after the program and four to six weeks following the program were statistically significantly improved from baseline testing, although there was a decline in scores four to six weeks after the program. These findings demonstrate effective knowledge transfer (recall of the information) immediately after the education program and four to six weeks later. Specific qualitative and quantitative data serve as a basis for understanding caregivers' needs and experiences.

Thyroid nodules (TN) are a common clinical problem. Fine needle aspiration (FNA) of the thyroid now is practiced worldwide and proves to be the most economical and reliable diagnostic procedure to identify TNs that need surgical excision and TNs that can be managed conservatively. The key for the success of thyroid FNA consists of an adequate or representative cell sample and the expertise in thyroid cytology. The FNA cytologic manifestations of TNs may be classified into seven working cytodiagnostic groups consisting of a few heterogenous lesions each to facilitate the differential diagnosis. Recent application of diagnostic molecular techniques to aspirated thyroid cells proved to be useful in separating benign from malignant TNs in several cases of indeterminate lesions.

The Rho GDP dissociation inhibitor (GDI) is an ubiquitously expressed regulatory protein involved in the cycling of Rho proteins between membrane-bound and soluble forms. Here, we characterized the Rho solubilization activity of a glutathione S-transferase (GST) - GDI fusion protein in a cell-free system derived from rat kidney. Addition of GST-GDI to kidney brush border membranes resulted in the specific release of Cdc42 and RhoA from the membranes, while RhoB and Ras were not extracted. The release of Cdc42 and RhoA by GST-GDI was dose dependent and saturable with about 50% of both RhoA and Cdc42 extracted. The unextracted Rho proteins were tightly bound to membranes and could not be solubilized by repeated GST-GDI treatment. These results demonstrated that kidney brush border membranes contained two populations of RhoA and Cdc42. Furthermore, the GST-GDI solubilizing activity on membrane-bound Cdc42 and RhoA was abolished at physiological conditions of salt and temperature in all tissues examined. When using bead-immobilized GST-GDI, KCl did not reduced the binding of Rho proteins. However, washing brush border membranes with KCl prior treatment by GST-GDI inhibited the extraction of Rho proteins. Taken together, these results suggest that the binding of GDI to membrane-bound Cdc42 and RhoA occurs easily under physiological ionic strength conditions, but a complementary factor is required to extract these proteins from membranes. These observations suggest that the shuttling activity of GDI upon Rho proteins could be normally downregulated under physiological conditions.

Research on the importance of genetic and environmental risk factors (multifactorial) in the etiology of mental disorders and substance use disorders (alcoholism) is now growing rapidly. Biological and psychological studies in this field should include basic concepts of medical genetics and take heterogeneity (multidimensionality) of mental disorders into account. One of the best means to cope with heterogeneity is to redefine the diagnostic phenotype at different levels: biochemical, behavioral, familial. Data are presented where the introduction of different quantitative definitions of the phenotype and their analysis by multivariate technics are used for better understanding of alcoholic disorders.