Physical Activity and Sedentary Behavior of Elderly Populations during Confinement: Results from the FRENCH COVID-19 ONAPS Survey.

Introduction: A national confinement was imposed in France in March 2020 during 55 days to prevent the spread of the virus and protect vulnerable people such as older individuals. This study aimed to describe the movement behaviors, and their determinants, of elderly people (≥ 65 years) during the confinement.Methods: An online survey was conducted from April 1st, 2020 to May 6th, 2020 by the National Observatory for Physical Activity and Sedentary behaviors. This study compared the level of physical activity (PA), sitting and screen time before and during the confinement and identified the impact of initial PA, sedentary profiles of the participants and housing conditions.Results: 1,178 people were included in this study. Reaching PA recommendations before lock-down was associated with the change in PA level during lock-down (p < .001). Besides, geographic location was associated with the change in PA, sitting time and screen time during lock-down (respectively p = .03, p = .02, p = .02).Conclusion: This study confirm the negative impact of confinement on senior movement behaviors, whether or not they met with public health recommendations prior to the pandemic. The housing conditions of older people must be also taken into future public health policies.

Effect of the COVID-19 lockdown on physical activity and sedentary behaviors in French children and adolescents: New results from the ONAPS national survey.

INTRODUCTION: In France March 14, 2020 a national lockdown was imposed in France for 55 days to prevent the spread of COVID-19 and all schools were closed. This study aimed to investigate the effects of home confinement as a result of  lockdown on the activity (physical activity and sedentary behaviors), and their determinants, on French children (6-10 years) and adolescents (11-17 years). METHODS: The National Observatory for Physical Activity and Sedentary behaviors launched an online survey from April 1st, to May 6th, 2020 using popular social networks and websites. It compared the level of physical activity (PA), sitting and screen time before and during the lockdown and identified the impact of the initial PA (active vs. inactive), sedentary (high vs. low) profiles of the participants and their housing conditions. RESULTS: 6,491 children were included in this study. Initially active children and adolescents decreased their PA more than those initially inactive (p>0.001), while those who met the sitting time recommendations increased more their sitting time during lockdown (p<0.001). The same applied to screen time (p<0.001). Living in an urban environment was associated with a decrease in PA (p<0.001), an increase in sitting time (p<0.001) and children's screen time (p=0.002) during lockdown. CONCLUSION: This study showed the deleterious effects of confinement caused by lockdown on physical activity and sedentary behaviors. Housing conditions were associated with lifestyle behaviors over this period of lockdown. Future public health policies should consider these results.

Satiety responsiveness but not food reward is modified in response to an acute bout of low versus high intensity exercise in healthy adults.

To compare the effect of iso-caloric low and high intensity exercises on Satiety Quotient and Food Reward in response to a fixed meal in healthy young adults. Anthropometric measurements, body composition (BIA), aerobic capacity (VO2 max) and food preferences were assessed in 19 healthy normal-weight young adults (21 ±â€¯0.5 years old, 10 men). They randomly completed 3 experimental sessions: i) control session without exercise (CON); ii) High Intensity exercise session (HIE); iii) Low intensity exercise session (LIE). Thirty minutes after exercise or rest, then received a fixed lunch. Food reward (Leeds Food Preference Questionnaire) was assessed before and after the meal. Appetite sensations were assessed at regular intervals, SQ was calculated from the lunch meal and self-reported food intake was collected for the rest of the day. Mean body weight was 66.7 ±â€¯9.2 kg, body mass index was 22.3 ±â€¯2.9 kg/m2 and FM% was 18.7 ±â€¯6.8%. Appetite feelings did not differ between conditions and were not affected by exercise. SQ for satiety was not different between conditions. SQ hunger on CON was significantly higher than on LIE and HIE (p ≤ 0.05) with no difference between exercise conditions. SQ for desire to eat was significantly higher on CON versus HIE (p ≤ 0.01) with no differences between CON and LIE and between exercise sessions. SQ PFC was significantly lower on HIE compared with CON (p = 0.02) with no differences between LIE and CON and between LIE and HIE. Food reward was not significantly different between the three condition as well as self-reported total food and macronutrient intake for the rest of the days. Acute exercise, depending on its intensity, might affect the satiating response to food intake in healthy adults, without altering food reward.

Employees' adherence to worksite physical activity programs: Profiles of compliers versus non-compliers.

While worldwide public health policies have emphasized the necessity to create a culture that favors regular physical activity, stakeholders and health institutions keep looking for new strategies and opportune settings. Workplaces have been identified since employees spent a considerable part of their time at work and several worksite interventions have been developed lately. While the actual scientific literature clearly points out the beneficial effects of physical activity programs implemented within companies on employees overall health, available evidences however seem to question their adherence to such interventions. Based on previously published results and new observations, this paper discusses the adherence rate during workplace physical activity programs and suggests new strategies to favor increased physical activity among employees, considering their dropouters or finishers' profiles.

Lean adolescents achieve higher intensities but not higher energy expenditure while playing active video games compared with obese ones.

BACKGROUND: While decreased physical activity and increased sedentary behaviours are incriminated for their role in the progression of obesity, active video games (AVG) may offer a new alternative to increase energy expenditure in youth. This study is the first to examine the effect of a 1-h AVG play on lean and obese adolescents' energy expenditure. METHODS: Body composition and aerobic fitness were assessed in 19 obese and 12 lean adolescent boys (12-15 years old). Participants performed a 1-h AVG session (Kinect Sports technology) while wearing a portable indirect calorimeter (K4b2) to assess their energy expenditure and heart rate. RESULTS: Body weight (91.0 ± 9.5 vs. 58.5 ± 12.4 kg), body mass index (32.2 ± 3.1 vs. 20.3 ± 1.6 kg m(-2) ) and body fat (38.1 ± 2.7 vs. 13.4 ± 3.9%) were significantly higher in obese adolescents (P < 0.001). Absolute energy expenditure was significantly higher in obese (P < 0.05) but not when corrected for body composition. Maximal heart rate reached during AVG was significantly higher in lean adolescents (190 ± 25 vs. 183 ± 28 bpm, P < 0.05). Time spent between 3 and 6 METs (Metabolic Equivalent Task) was not different between groups but time spent above 6 METs was higher in lean adolescents (P < 0.05). CONCLUSION: Although lean and obese adolescent boys experienced similar energy expenditure relative to their body size during a 1-h Kinect AVG session, lean adolescents spent more time in moderate-to-vigorous physical activity.

Reduced neural response to food cues following exercise is accompanied by decreased energy intake in obese adolescents.

BACKGROUND: Acute exercise has been found to favor a transient anorexigenic effect in obese adolescents. Although the role of some gastro-peptides has been suggested as an explanation for this observed reduced energy intake after exercise, it is unknown whether neural pathways involved in the regulation of food intake are modulated in youth. METHODS: Body composition (dual-energy X-ray absorptiometry) and aerobic capacities were assessed in 19 obese adolescent boys. Participants were randomized to remain at rest in a sitting position (CON condition) or to exercise 45 min at 65% of their maximal capacities (EX condition) by the end of the morning. An attentional computer task with electroencephalography recording was completed immediately after the exercise or sitting period to measure an event-related component (P3b) reflecting the level of cognitive engagement in the processing of food cues. A lunch test-meal was offered ad libitum and appetite feelings assessed at regular intervals using visual analog scales. RESULTS: The 45-min cycling exercise set at 65% VO2max induced a mean energy expenditure of 399±75 kcal. Both absolute (P<0.05) and relative (P<0.001) subsequent energy intake were significantly reduced after EX (1037±260 and 639±256 kcal, respectively) compared with CON (1116±243 and 1011±239 kcal, respectively). The energy ingested derived from each macronutrient and self-reported appetite remained unchanged. Although the amplitudes of the P3b component evoked by food and non-food visual stimuli were not significantly different during CON, the response to food cues was significantly reduced compared with non-food stimuli after exercise (P<0.01). DISCUSSION: An acute exercise favors decreased neural response to food cues compared with non-food ones in obese adolescents that may contribute to their subsequently reduced energy intake.

Breast microcalcifications: the lesions in anatomical pathology.

Microcalcifications are actually indirect signs of pathological processes, and only a few of these processes may be correctly correlated to the morphologic pattern of calcifications. This is true of the microcalcifications typically classified as benign by the 4th edition of the BI-RADS Atlas, except for round and punctuate microcalcifications. This is also the case of polymorphous fine and linear fine microcalcifications most often, but not exclusively, associated with DCIS with necrosis. For other types of microcalcifications, other parameters are analyzed in a more global approach: the associated clinical or mammographical signs; the context, especially genetic; the spatial distribution; the number; the evolution over time. The radiologist should compare the images with the anatomy of the terminal ductal-lobular unit, from where most cancers arise, and estimates the risk by taking into account the clinical context and the antecedents.

Using one-step nucleic acid amplification (OSNA) for intraoperative detection of lymph node metastasis in breast cancer patients avoids second surgery and accelerates initiation of adjuvant therapy.

BACKGROUND: Sentinel lymph node (SLN) analysis is conventionally analyzed using immunohistochemistry and in the case of SLN involvement, justifies a second surgery for axillary lymph node (ALN) resection, thus delaying the initiation of adjuvant therapies. PATIENTS AND METHODS: Three hundred and eighty-one patients with early stage breast cancer (BC) were considered in this retrospective study. SLNs were detected using combined radioisotope and dye detection. SLN involvement was analyzed using routine intraoperative One-Step Nucleic Acid Amplification (OSNA) assay, in 100 patients and compared with the conventional histopathology carried out previously in 281 patients. RESULTS: Considering positive SLNs as '++' (CK19 mRNA copy number>5000), '+' (250 < CK19 mRNA copy number <5000) and positive by inhibition in the OSNA group and macro-, micrometastases and isolated tumor cells in the histopathology group, no difference in SLN involvement rate was found between the two groups with 29.0% and 29.9% of positive SLNs, respectively. Using OSNA intraoperatively, the mean time to process the SLN was 42 min allowing immediate ALN resection, reduced significantly (P < 0.01) the re-intervention rate (9% versus 39%) and significantly (P < 0.01) accelerated the initiation of adjuvant therapy (6.2 versus 8.4 weeks). CONCLUSIONS: Using OSNA for intraoperative SLN analysis avoids second surgery for ALN resection in most patients and accelerates initiation of adjuvant therapy.

Analysis of correlation between mitotic index, MIB1 score and S-phase fraction as proliferation markers in invasive breast carcinoma. Methodological aspects and prognostic value in a series of 257 cases.

BACKGROUND: The study was designed in order to evaluate the degree of correlation of mitotic index (MI), Ki67 (MIB1) score and S-phase fraction (SPF) as markers of cell proliferation and prognosis in breast cancer. MATERIALS AND METHODS: The series analysed corresponded to 257 consecutive invasive breast carcinoma, treated at the Institut Curie, France, in 1995. Nottingham histological grade and MIB1 semiquantitative and quantitative score were assessed on histological sections, whereas SPF was calculated using flow cytometry analysis of fine-needle aspiration products. Proliferation indices were compared to pathological data and to overall survival (OS) and disease-free survival (DFS) (minimum follow-up: 72 months). RESULTS: The median values for the proliferation markers were 9/10 HPF for MI, 32.4% for MIB1 and 3.7% for SPF. A high rate of correlation (r=0.96; p<0.001) was observed between semi-quantitative and quantitative MIBI evaluation. A positive correlation was found between the three markers (r ranging from 0.54 to 0.61;p<0.001). Univariate analysis of markers associated to disease outcome showed that MIB1, axillary node status (N) and progesterone receptor (PR) status were significantly associated with OS and that MIB1 and SPF were associated with DFS, together with node and hormone receptor status. In multivariate analysis, when proliferation markers were adjusted on the N and PR status, only MIB1 retained a prognostic value for OS (RR= 1.83) [1.00;3.35] and SPF for DFS (RR= 1.58) [1.02-2.44] (p=0.04). CONCLUSION: A good level of correlation was observed between the values of the three markers of tumour cell proliferation analysed. In this series of invasive breast cancers, MIB1 immunostaining was found to be a prognostic marker of both OS and DFS. The median (32.4%) was a valuable cut-off value for prognostic assessment. Semi-quantitative and quantitative evaluations provided very similar values. MIB1 can thus be considered as a reliable prognostic maker, usable in small size tissue specimens which are inappropriate for MI or SPF analysis. The impact of MIB1 compared to that of the other proliferative markers will be further assessed in a subgroup of T1N0M0 for which the prognostic assessment is of major interest.

Increased cell size and Akt activation in HER-2/neu-overexpressing invasive ductal carcinoma of the breast.

AIMS: To determine whether cell size is related to HER-2/neu status and/or to Akt activation in breast carcinomas. HER-2/neu overexpression is observed in 20-30% of invasive breast carcinomas with poor pronostic features, but little is known about the cell phenotype associated with HER-2/neu activation. Akt has been found to be involved in the HER-2/neu signal transduction pathway and Akt activation has been associated with increased cell size in various models. METHODS AND RESULTS: A case-control study of invasive ductal carcinoma of the breast was carried out, including 21 cases displaying HER-2/neu overexpression and 20 HER-2/neu negative controls. Cytoplasmic and nuclear sizes were measured on digitized histological pictures using cell image analysis software. Akt expression analysis was performed by immunohistochemistry on formalin-fixed histological sections using an anti-phosphorylated-Akt (Ser473) antibody. RESULTS: HER-2/neu-overexpressing carcinomas had a mean nuclear size of 75 +/- 22.2 micro m(2) and a mean cytoplasmic size of 187 +/- 52.3 micro m(2). Both values were higher than the nuclear and cytoplasmic size of HER-2/neu-negative cases (nucleus = 58 +/- 24.5 micro m(2), cytoplasm = 133 +/- 56.6 micro m(2); P = 0.02 and P =0.003, respectively). Up to 75% of the tumours with a cell size over 140 micro m(2) were HER-2/neu-positive. Immunohistochemical Akt expression was observed in 19/40 (47.5%) cases. The immunoreactivity was localized in the cytoplasm in eight cases, on the cell membrane in four cases and at both sites in seven cases. One case was not interpretable. Comparison between HER-2/neu and Akt status showed that Akt was detectable at the cell membrane in 43% (9/21) of HER-2/neu-positive and in 10% (2/19) of HER-2/neu-negative cases (P = 0.02). CONCLUSIONS: HER-2/neu overexpression was consistently associated with increased cell size in invasive ductal carcinoma of the breast. This increase may be related to concomitant Akt activation. The assessment of activated pathways in HER-2/neu-overexpressing breast carcinomas may provide useful information for optimized individual HER-2/neu-targeted therapy.

Wide metastatic spreading in infiltrating lobular carcinoma of the breast.

The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin em leader ) (P<0.001). In ILC, no significant link was found between the localisation(s) of metastases, the histological subtype and the EC status in the primary. In conclusion, in breast carcinomas, the frequency of multiple metastasis was found to be higher in ILC than IDC. This fact may be related to the phenotypic trait of discohesive small cells which characterises ILC. EC loss, observed in most cases of ILC, may result in alterations in cell-cell adhesion and a preferential growth at metastatic sites. A high rate of pleomorphic tumours was observed in the group of metastatic ILC, but the pattern of metastatic site(s) was not related to the histological subtype of the primary.

[Histological margin and residual disease assessment for breast carcinoma]. / Evaluation des limites d'exérèse chirurgicale en pathologie mammaire. Risque de maladie résiduelle.

Margin and histological size of ductal in situ carcinoma or intraductal component of an infiltrative carcinoma are important prognostic factors to predict presence/absence as well as amount of residual tumor burden. Their evaluation requires standardized pathological analysis. These factors should be interpreted in clinical and radiological context.

Disruption of NF-kappa B signaling and chemokine gene activation by retroviral mediated expression of IKK gamma/NEMO mutants.

Phosphorylation of I kappa Bs--the cytoplasmic inhibitors of the NF-kappa B transcription factors--is the key event which triggers activation of the NF-kappa B cascade. Signal-mediated phosphorylation of I kappa B alpha is mediated by a multiprotein complex, the I kappa B kinase (IKK) complex, which is composed of at least three identified subunits. Two of these polypeptides, IKK alpha and IKK beta, also known as IKK1 and IKK2, are the catalytic subunits of the kinase complex and phosphorylate I kappa B alpha and I kappa B beta. The third component, NEMO/IKK gamma, does not exhibit kinase activity, but rather constitutes a regulatory subunit. In the present study, C-terminal truncated forms of IKK gamma--Delta C-IKK gamma 306 and Delta C-IKK gamma 261--were stably expressed in the myeloid cell line U937 by retroviral-mediated gene transfer. Overexpression of Delta C-IKK gamma resulted in a reduction in IKK kinase activity in vitro, a subsequent decrease in NF-kappa B DNA binding activity, and inhibition of chemokine gene induction in response to TNFalpha stimulation or paramyxovirus infection. This study demonstrates the efficacy of Delta C-IKK gamma as a repressor of IKK signaling and NF-kappa B activation and suggests a potential gene therapy approach to limit chronic inflammation due to chemokine hyperactivation.

HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators.

Human herpes virus 8 (HHV-8) has developed unique mechanisms for altering cellular proliferative and apoptotic control pathways by incorporating viral homologs to several cellular regulatory genes into its genome. One of the important pirated genes encoded by the ORF K9 reading frame is a viral homolog of the interferon regulatory factors (IRF), a family of cellular transcription proteins that regulates expression of genes involved in pathogen response, immune modulation and cell proliferation. vIRF-1 has been shown to downregulate the interferon- and IRF-mediated transcriptional activation of ISG and murine IFNA4 gene promoters. In this study we demonstrate that vIRF-1 efficiently inhibited virus-induced expression of endogenous interferon B, CC chemokine RANTES and CXC chemokine IP-10 genes. Co-expression analysis revealed that vIRF-1 selectively blocked IRF-3 but not IRF-7-mediated transactivation. vIRF-1 was able to bind to both IRF-3 and IRF-7 in vivo as detected by coimmunoprecipitation analysis, but did not affect IRF-3 dimerization, nuclear translocation and DNA binding activity. Rather, vIRF-1 interacted with the CBP/p300 coactivators and efficiently inhibited the formation of transcriptionally competent IRF-3-CBP/p300 complexes. These results illustrate that vIRF-1 is able to block the early stages of the IFN response to virus infection by interfering with the activation of IRF-3 responsive, immediate early IFN genes.

Selective DNA binding and association with the CREB binding protein coactivator contribute to differential activation of alpha/beta interferon genes by interferon regulatory factors 3 and 7.

Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and IRF-7 as key activators of the alpha/beta IFN (IFN-alpha/beta) genes as well as the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1, and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4, IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric proteins containing combinations of different IRF-7 and IRF-3 domains were also tested, and the results provided evidence of distinct DNA binding properties of IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB binding protein (CBP) coactivator. Interestingly, some of these fusion proteins led to supraphysiological levels of IFN promoter activation. DNA binding site selection studies demonstrated that IRF-3 and IRF-7 bound to the 5'-GAAANNGAAANN-3' consensus motif found in many virus-inducible genes; however, a single nucleotide substitution in either of the GAAA half-site motifs eliminated IRF-3 binding and transactivation activity but did not affect IRF-7 interaction or transactivation activity. These studies demonstrate that IRF-3 possesses a restricted DNA binding site specificity and interacts with CBP, whereas IRF-7 has a broader DNA binding specificity that contributes to its capacity to stimulate delayed-type IFN gene expression. These results provide an explanation for the differential regulation of IFN-alpha/beta gene expression by IRF-3 and IRF-7 and suggest that these factors have complementary rather than redundant roles in the activation of the IFN-alpha/beta genes.

Regulation of RANTES chemokine gene expression requires cooperativity between NF-kappa B and IFN-regulatory factor transcription factors.

Virus infection of host cells activates a set of cellular genes, including cytokines, IFNs, and chemokines, involved in antiviral defense and immune activation. Previous studies demonstrated that virus-induced transcriptional activation of a member of the human CC-chemokine RANTES required activation of the latent transcription factors IFN-regulatory factor (IRF)-3 and NF-kappa B via posttranslational phosphorylation. In the present study, we further characterized the regulatory control of RANTES transcription during virus infection using in vivo genomic footprinting analyses. IRF-3, the related IRF-7, and NF-kappa B are identified as important in vivo binding factors required for the cooperative induction of RANTES transcription after virus infection. Using fibroblastic or myeloid cells, we demonstrate that the kinetics and strength of RANTES virus-induced transcription are highly dependent on the preexistence of IRFs and NF-kappa B. Use of dominant negative mutants of either I kappa B-alpha or IRF-3 demonstrate that disruption of either pathway dramatically abolishes the ability of the other to bind and activate RANTES expression. Furthermore, coexpression of IRF-3, IRF-7, and p65/p50 leads to synergistic activation of RANTES promoter transcription. These studies reveal a model of virus-mediated RANTES promoter activation that involves cooperative synergism between IRF-3/IRF-7 and NF-kappa B factors.

Interferon activation and innate immunity.

The interferons are a family of cytokine mediators critically involved in alerting the cellular immune system to viral infection of host cells. Interferons not only exhibit important antiviral effects but also exert a key influence on the quality of the cellular immune responses and amplify antigen presentation to specific T cells. Type I interferon (IFN-alpha and IFN-beta) is secreted by virus-infected cells while type II, immune or gamma interferon (IFN-gamma) is mainly secreted by T cells, natural killer (NK) cells and macrophages. Interferons interact with specific cellular receptors, which promote production of second messengers ultimately leading to expression of antiviral and immune modulatory genes. The IFN genes themselves are regulated by transcriptional and posttranscriptional mechanisms including modulation by a family of interferon regulatory factors (IRFs) synthesised by host cells. IFNs activate macrophages, induce B cells to switch immunoglobulin type, alter T helper response, inhibit cell growth, promote apoptosis and induce an antiviral state in uninfected cells. The therapeutic potential of the IFNs is currently the focus of intense attention in a number of virus-associated diseases, tumours and autoimmune disorders.

Interferon regulatory factors: the next generation.

Interferons are a large family of multifunctional secreted proteins involved in antiviral defense, cell growth regulation and immune activation. Viral infection induces transcription of multiple IFN genes, a response that is in part mediated by the interferon regulatory factors (IRFs). The initially characterized members IRF-1 and IRF-2 are now part of a growing family of transcriptional regulators that has expanded to nine members. The functions of the IRFs have also expanded to include distinct roles in biological processes such as pathogen response, cytokine signaling, cell growth regulation and hematopoietic development. The aim of this review is to provide an update on the novel discoveries in the area of IRF transcription factors and the important roles of the new generation of IRFs--particularly IRF-3, IRF-4 and IRF-7.