Purpose
Exercise has been shown to have various proximal and distal benefits among older adults such as improving physical fitness, cognitive functioning, and health-related quality of life (HR-QOL). ...Despite this evidence, limited research has investigated pathway change of these outcomes. The primary purpose of this study was to test if older adults who improved in physical fitness measures from engaging in multicomponent exercise training for 12 weeks predicted change in proximal (cognitive functioning) and distal (HR-QOL) outcomes, respectively.
Methods
Participants (
n
= 110) were healthy, older adults (
M
= 72, SD = 7.24) that comprised an exercise-intervention and control group. The intervention consisted of exercising in a supervised laboratory setting for 12 weeks.
Results
Structural equation modeling revealed group type to predict change in physical performance and the maximum walking test with comparable effect sizes. Physical performance in turn predicted improvement in processing speed (
β
= 0.23,
p
= 0.013) executive functioning (
β
= 0.26,
p
= 0.006), and HR-QOL (
β
= 0.13,
p
= 0.031). However, only executive functioning was found to significantly predict HR-QOL (
β
= 0.49,
p
< 0.001) over processing speed (
p
> 0.05).
Conclusions
Between two fitness measures, the physical performance test demonstrated better predictive validity in proximal and distal health outcomes. In addition to physical fitness, older adults who engage in multi-component exercise sessions regularly can improve their executive functioning, which in turn enhances their HR-QOL.
To describe the efficacy of conservative management of retinoblastoma by an association of conservative ocular therapies and chemothermotherapy.
Phase II prospective nonrandomized trial.
Eighty-three ...children were included (115 eyes).
Conservative ocular therapies and chemothermotherapy (intravenous carboplatin followed by transpupillary thermotherapy to the tumor) after chemoreduction by 2 cycles of carboplatin and etoposide.
Use of external beam therapy and ocular tumor control.
One hundred fifteen of the 147 affected eyes were eligible for conservative management. Nineteen children had unilateral lesions (22.8%), and 64 (77.1%) had bilateral lesions. Sixty-six children received neoadjuvant chemotherapy before ocular therapy, which consisted of one or a combination of several techniques: chemothermotherapy (65 children 86 eyes) with a mean of 3 cycles per child, thermotherapy alone (22 children 24 eyes), cryoapplication (49 children 58 eyes), and iodine 125 brachytherapy (26 children 29 eyes). Tumor control was achieved for 97 eyes (84%). At the end of the study, external beam radiotherapy (EBR) was necessary for a total of 9 children (11%) and 13 eyes (12%). Enucleation was necessary for a total of 23 eyes (20%), because of complications in 5 cases.
Neoadjuvant chemotherapy with 2 cycles of carboplatin and etoposide followed by ocular therapy and chemothermotherapy achieves satisfactory tumor control and permits a low need for EBR.
Background
Half of the people with fear of falling (FoF) are non-fallers, and the reason why some people considered non-fallers are afraid of falling is unknown, but reduced mobility or cognition, or ...both concurrently must be considered as potential risk factors.
Aim
The study aimed to determine if mobility and/or cognitive abilities could identify people with a history of falls in older adults with FoF.
Methods
Twenty-six older adults with FoF participated in this study. Full cognitive and mobility assessments were performed assessing global cognitive impairments (MoCA score < 26), executive functions, memory, processing speed, visuospatial skills, mobility impairment (TUG time > 13.5 s), gait, balance and physical capacity. Information about falls occurring during the year prior to the inclusion was collected. Logistic regression analyses were performed to explore the association between falls and cognitive and mobility abilities.
Results
No significant differences in age, sex, level of education or body mass index were detected between fallers and non-fallers. Cognitive impairments (MoCA score < 26) distinguished between fallers and non-fallers (
p
= 0.038;
R
2
= 0.247). Among specific cognitive functions, visuospatial skills distinguished between fallers and non-fallers (
p
= 0.027;
R
2
= 0.258). Mobility impairments (TUG time > 13.5 s), gait, balance and physical capacity were not related to past falls.
Discussion/conclusion
In older adults with FoF, global cognitive deficits detected by the MoCA are important factors related to falls and more particularly visuospatial skills seem to be among the most implicated functions. These functions could be targeted in multifactorial interventions.
Obesity is associated with an accelerated cognitive decline. Aerobic fitness has a protective effect on cognition in older adults, but no study has investigated this effect in obese individuals. The ...present study aimed to 1) compare cognitive function in lower-fit (LoFit) and higher-fit (HiFit) obese individuals compared with nonobese individuals, and 2) examine the association between exercise variables (including hemodynamic variables) and cognitive function in obese individuals.
Fifty-four obese and 16 nonobese individuals performed a maximal cardiopulmonary exercise test (with gas exchange analysis and noninvasive hemodynamic measurement) and cognitive tests assessing short-term and working memory, processing speed, executive function, and long-term verbal memory. Obese individuals were divided into 2 groups according to their median aerobic fitness divided by lean body mass to form a group of LoFit obese (n = 27) and a group of HiFit obese (n = 27) individuals.
A total of 14 nonobese individuals and 49 obese individuals were included in the final analysis (HiFit: n = 26, LoFit: n = 23). Compared with LoFit obese, HiFit obese participants had greater performances in executive function (P = 0.002) and short-term memory (P = 0.02). Nonobese and HiFit obese participants showed equivalent performances in all domains of cognition. In obese individuals, aerobic fitness was the only independent predictor for short-term memory (R2 = 0.24; P < 0.001), working memory (R2 = 0.16; P = 0.02), processing speed (R2 = 0.22; P = 0.01), and executive function (R2 = 0.49; P = 0.003), but not for long-term verbal memory (R2 = 0.15; P = 0.26).
HiFit obese individuals showed greater short-term memory and executive function performances compared with LoFit obese individuals, suggesting that aerobic fitness could help preserve cognitive function despite the presence of obesity.
L’obésité est associée à un déclin cognitif accéléré. L’aptitude aérobie a un effet protecteur sur la cognition des personnes âgées, mais aucune étude n’a montré cet effet chez les individus obèses. La présente étude avait pour but de : 1) comparer les performances cognitives des individus obèses en moins bonne forme physique (LoFit, de l’anglais lower-fit) et en meilleure forme physique (HiFit, de l’anglais higher-fit) aux individus non obèses; 2) d’examiner l’association entre les variables physiques (y compris les variables hémodynamiques) et les performances cognitives chez les individus obèses.
Cinquante-quatre individus obèses et 16 individus non obèses ont effectué une épreuve d’effort cardiopulmonaire maximal (avec analyse des échanges gazeux et mesures hémodynamiques non invasives) et des épreuves cognitives évaluant la mémoire à court terme et de travail, la vitesse de traitement, la fonction exécutive et la mémoire verbale à long terme. Nous avons réparti les individus obèses en 2 groupes selon la médiane de l'aptitude aérobie divisée par la masse corporelle maigre pour former un groupe d’individus obèses en moins bonne forme physique (LoFit, n = 27) et un groupe d’individus obèses en meilleure forme physique (HiFit, n = 27).
Nous avons inclus un total de 14 individus non obèses et 49 individus obèses dans l’analyse finale (HiFit : n = 26, LoFit : n = 23). Comparativement aux participants obèses en moins bonne forme physique, les participants obèses en meilleure forme physique avaient de meilleures performances dans la fonction exécutive (P = 0,002) et dans la mémoire à court terme (P = 0,02). Les participants non obèses et les participants obèses en meilleure forme physique montraient des performances équivalentes dans toutes les sphères de la cognition. Chez les individus obèses, l’aptitude aérobie était le seul prédicteur indépendant de la mémoire à court terme (R2 = 0,24; P < 0,001), de la mémoire de travail (R2 = 0,16; P = 0,02), de la vitesse de traitement (R2 = 0,22; P = 0,01) et de la fonction exécutive (R2 = 0,49; P = 0,003), mais non de la mémoire verbale à long terme (R2 = 0,15; P = 0,26).
Les individus obèses en meilleure forme physique montraient de meilleures performances dans la mémoire à court terme et dans la fonction exécutive que les individus obèses en moins bonne forme physique. Ces constatations montrent que l’aptitude aérobie pourrait contribuer à préserver les performances cognitives en dépit de la présence de l’obésité.
Uveal melanoma (UM) is associated with a high risk of metastases and lack of efficient therapies. Reduced capacity for apoptosis induction by chemotherapies is one obstacle to efficient treatments. ...Human UM is characterized by high expression of the anti-apoptotic protein Bcl-2. Consequently, regulators of apoptosis such as Bcl-2 family inhibitors may constitute an attractive approach to UM therapeutics. In this aim, we have investigated the efficacy of the Bcl-2/Bcl-XL inhibitor S44563 on 4 UM Patient-Derived Xenografts (PDXs) and derived-cell lines.
Four well characterized UM PDXs were used for in vivo experiments. S44563 was administered alone or combined with fotemustine either concomitantly or after the alkylating agent. Bcl-2, Bcl-XL, and Mcl-1 expressions after S44563 administration were evaluated by immunohistochemistry (IHC).
S44563 administered alone by at 50 and 100 mg/kg i.p. induced a significant tumour growth inhibition in only one xenograft model with a clear dose effect. However, when S44563 was concomitantly administered with fotemustine, we observed a synergistic activity in 3 out of the 4 tested models. In addition, S44563 administered after fotemustine induced a tumour growth delay in 2 out of 3 tested xenografts. Finally, IHC analyses showed that Bcl-2, Bcl-XL, and Mcl-1 expression were not modified after S44563 administration.
The novel anti-apoptotic experimental compound S44563, despite a relative low efficacy when administered alone, increased the efficacy of fotemustine in either concomitant or sequential combinations or indeed subsequent to fotemustine. These data support further exploration of potential therapeutic effect of Bcl-2/Bcl-xl inhibition in human UM.
The 2018 Ocular Oncogenesis and Oncology Conference was held through a partnership of the Association for Research in Vision and Ophthalmology (ARVO) and the Champalimaud Foundation. Twenty-one ...experts from international ocular oncology centers, from the Champalimaud Clinical Centre and the Champalimaud Foundation Cancer Research Program, and from patient advocacy organizations, delivered lectures on subjects that ranged from global ocular oncology, to basic research in mechanisms of ocular malignancy, to clinical research in ocular cancers, and to anticipated future developments in the area. The scientific program of the conference covered a broad range of ocular tumors-including uveal melanoma, retinoblastoma, ocular surface tumors, and adnexal and intraocular lymphomas-and pathogenesis and management were deliberated in the context of the broader systemic cancer discipline. In considering the latest basic and clinical research developments in ocular oncogenesis and oncology, and providing the opportunity for cross-talk between ocular cancer biologists, systemic cancer biologists, ocular oncologists, systemic oncologists, patients, and patient advocates, the forum generated new knowledge and novel insights for the field. This report summarizes the content of the invited talks at the 2018 ARVO-Champalimaud Foundation Ocular Oncogenesis and Oncology Conference.
•Younger and older adults’ prefrontal cortex activity was compared with NIRS in a DT.•Instructions to give equal priority to both tasks or to prioritize one were given.•Priority effects were linked ...with distinct age-related patterns of activation.•Older adults show a more spread out activation when instructed to give equal priority.
Age-related differences in the ability to perform two tasks simultaneously (or dual-task) have become a major concern in aging neurosciences and have often been assessed with two distinct paradigms; the Psychological Refractory Period (PRP) and the Dual-Task (DT) paradigms. PRP studies assess participants when they give Priority to one task over the other (complete A then B), whereas in DT studies participants give Equal priority to both tasks (complete A and B). The Equal condition could be viewed as adding an executive control component to the task since the participants must spontaneously monitor attention between tasks. In the current study, we assessed the effect of priority instructions (Priority vs. Equal) on the dual-task performance and brain activity of younger (n=16) and older adults (n=19) with functional near infra-red spectroscopy (fNIRS). In younger adults, the Priority condition showed right-sided activation in the prefrontal cortex during DT execution. Older adults showed bilateral frontal activation, yet restrained to specific areas. They showed increased activation in DT vs. single task condition in the left dorsolateral prefrontal cortex (DLPFC) and the bilateral ventrolateral prefrontal cortex (VLPFC). In the Equal condition, the DT condition showed isolated left DLPFC and VLPFC activation in younger adults and widespread bilateral DLPFC activation in older adults. These results suggest that for both older and younger adults, priority effects are associated with distinct patterns of prefrontal activation. Age-related differences also exist in these patterns such that prefrontal activation seems to be more spread out at different sites in older adults when they are instructed to give Equal priority to both tasks.
To report a case of locally recurrent spindle-cell iris amelanotic melanoma 16 years after proton-beam therapy.
In 2001, a 45-year-old man presented with an amelanotic iris melanoma, extending from ...the 5 to 10 o'clock positions on his left eye. High-frequency ultrasonography showed extension of melanoma into the ciliary body. He was initially managed with proton-beam therapy (60 Gy delivered in four fractions over four consecutive days) and underwent ocular and systemic examination at regular intervals over the following years. Local tumor control was achieved, and the patient did not develop metastasis during sixteen consecutive years. In 2017, 16 years after he received proton-beam therapy, the patient developed a focal amelanotic lesion strongly suggestive of a local recurrence of iris melanoma, although it extended from the 1 to 6 o'clock positions. He also presented with treatment-resistant glaucoma with an intraocular pressure (IOP) of 37 mmHg, despite maximal topical IOP-lowering therapy. Since a second irradiation of the anterior segment was contraindicated, the eye was enucleated. Pathological analysis confirmed the diagnosis of iris melanoma and demonstrated iridocorneal angle invasion extending from the initial site to the recurrent tumor location.
Regular ophthalmological surveillance for life with gonioscopy and high-frequency ultrasonography is recommended in patients with iris melanoma, due to the possibility of delayed local recurrence more than a decade after the initial treatment.
Retinoblastoma is usually curable in developed countries. The morbidity and mortality of patients with hereditary retinoblastoma is still threatened by the occurrence of secondary tumours. Between ...1971 and 1988, 427 patients with retinoblastoma were treated in the ophthalmologic, paediatric and radiotherapy departments of the Institut Curie. In this study, we report the clinical and therapeutic features and the outcome of 25 patients treated for a second malignant neoplasm, diagnosed between 1997 and 1999 at the Institut Curie. The median time interval between the diagnosis of retinoblastoma and SMN was 11.2 years (range 3.8–20.6 years). Histopathological diagnoses included: 12 osteosarcomas, 12 soft tissue sarcomas and, 1 malignant oligodendroglioma. The second malignant neoplasm was located inside the radiation field in 21 cases and outside in 4. Twenty three patients received pre-operative chemotherapy. Surgery was performed in 16 patients. Post-operative chemotherapy was administered in 12 patients and external beam radiotherapy was used in 2 patients. Response to treatment was evaluable in 24 patients: complete remissions were observed in 14/24, partial remissions in 2/24 and progressive disease in 8/24. Nineteen patients died. Six are still alive, with 4 in complete remission (median follow-up 8.8 years; range 5.8–13.9 years). Despite aggressive therapy, the prognosis of patients with second malignant neoplasm occurring after retinoblastoma is very poor. It is important to provide information to retinoblastoma patients regarding the risk of a second tumour as this may facilitate an early tumour detection.
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