Liver transplant with controlled donors after circulatory death with normothermic regional perfusion and brain dead donors: A multicenter cohort study of transfusion, one-year graft survival and mortality.

BACKGROUND: Controlled donation after circulatory death (cDCD) has expanded the donor pool for liver transplantation (LT). However, transfusion requirements and perioperative outcomes should be elucidated. The aim of this multicenter study was to assess red blood cell (RBC) transfusions, one-year graft and patient survival after LT after cDCD with normothermic regional perfusion (NRP) compared with donors after brain death (DBD). METHODS: 591 LT carried out in ten centers during 2019 were reviewed. Thromboelastometry was used to manage coagulation and blood product transfusion in all centers. Normothermic regional perfusion was the standard technique for organ recovery. RESULTS: 447 patients received DBD and 144 cDCD with NRP. Baseline MCF Extem was lower in the cDCD group There were no differences in the percentage of patients (63% vs. 61% p = 0.69), nor in the number of RBC units transfused (4.7 (0.2) vs 5.5 (0.4) in DBD vs cDCD, p = 0.11. Twenty-six patients (6%) died during admission for LT in the DBD group compared with 3 patients (2%) in the cDCD group (p = 0.15). To overcome the bias due to a worse coagulation profile in cDCD recipients, matched samples were compared. No differences in baseline laboratory data, or in intraoperative use of RBC or one-year outcome data were observed between DBD and cDCD recipients. CONCLUSIONS: cDCD with NRP is not associated with increased RBC transfusion. No differences in graft and patient survival between cDCD and DBD were found. Donors after controlled circulatory death with NRP can increasingly be utilized with safety, improving the imbalance between organ donors and the ever-growing demand.

Suture pattern does not influence outcomes of endoscopic sleeve gastroplasty in obese patients.

Background and study aims ESG is an effective and safe medium-term procedure for obesity treatment. A variety of suture patterns have been reported. We aimed to compare whether there are differences in efficacy depending on suture pattern used. Patients and methods Retrospective and comparative review of 5 years of prospectively collected data, including consecutive obese patients undergoing ESG at two collaborative centers. Primary outcomes included weight loss (mainly % total body weight loss [TBWL] and % exces weight loss [EWL]) at 12 months and safety profile. We compared them according to three suture patterns (transverse bilinear [TBp], longitudinal [Lp] and transverse monolinear [TMp]), and number of sutures (4 - 7) and stitches (< 25, 25 to 30 and > 30) applied. Evolution of major obesity-associated morbidities (hypertension, dyslipidemia, Type 2 diabetes mellitus (T2DM), sleep obstructive apnea syndrome, and arthropathy) were also described. Results 88 patients (mean age 46.1±12.3 years, 69.3 % female) underwent ESG. Mean body mass index (BMI) at baseline was 39.40 ±â€Š4.69 kg/m². At 1 year, %TBWL was 17.36 ±â€Š6.09 % (%EWL 46.41±20.6 %) with TBWL > 10 % in 95.5 % of patients (EWL > 25 % in 94.3 % of patients). According to pattern, there were no differences in %TBWL but there were in %EWL (43.7 ±â€Š20.4 %, 59.8 ±â€Š18.9 % and 45.4 ±â€Š14.9 % in TBp, Lp and TMp patterns, respectively) ( P  = 0.034). No differences were found related to number of sutures (mean 5.2 ±â€Š0.73, r = 4 - 7) or stitches (mean 27.4 ±â€Š6.50, r = 18 - 50) applied. Forty-three of 72 (59.7 %) major comorbidities were resolved. No serious adverse events were observed with any pattern. Conclusions ESG is an effective procedure at 12-month follow-up for weight loss and comorbidity resolution. All three analyzed patterns are safe and effective without differences in %TBWL, but there was a slight increase in %EWL in Lp, regardless of the number of sutures or stitches applied.

Population structure of modern-day Italians reveals patterns of ancient and archaic ancestries in Southern Europe.

European populations display low genetic differentiation as the result of long-term blending of their ancient founding ancestries. However, it is unclear how the combination of ancient ancestries related to early foragers, Neolithic farmers, and Bronze Age nomadic pastoralists can explain the distribution of genetic variation across Europe. Populations in natural crossroads like the Italian peninsula are expected to recapitulate the continental diversity, but have been systematically understudied. Here, we characterize the ancestry profiles of Italian populations using a genome-wide dataset representative of modern and ancient samples from across Italy, Europe, and the rest of the world. Italian genomes capture several ancient signatures, including a non-steppe contribution derived ultimately from the Caucasus. Differences in ancestry composition, as the result of migration and admixture, have generated in Italy the largest degree of population structure detected so far in the continent, as well as shaping the amount of Neanderthal DNA in modern-day populations.

Development of a Novel Imaging Agent for Determining Albumin Uptake in Solid Tumors.

PURPOSE: The purpose of this study was to investigate the albumin-binding compound 111In-C4-DTPA as an imaging agent for the detection of endogenous albumin accumulation in tumors. METHODS: 111In-C4-DTPA was injected in healthy nude mice for pharmacokinetic and biodistribution studies (10 min, 1, 6, 24, and 48 h, n = 4) and subsequently in tumor-bearing mice for single-photon emission computed tomography/X-ray-computed tomography (SPECT/CT) imaging studies. Four different human tumor xenograft models (LXFL529, OVXF899, MAXFTN401, and CXF2081) were implanted subcutaneously unilaterally or bilaterally (n = 4-8). After intravenous administration of 111In-C4-DTPA, SPECT/CT images were collected over 72 h at 4-6 time points. Additionally, gamma counting was performed for the blood, plasma, lungs, heart, liver, spleen, kidneys, muscle, and tumors at 72 h post-injection. RESULTS: 111In-C4-DTPA bound rapidly to circulating albumin upon injection, and the radiolabeled albumin conjugate thus formed was stable in murine and human serum. SPECT/CT images demonstrated a time-dependent uptake with a maximum of 2.7-3.8% ID/cm3 in the tumors at approximately 24 h post-injection and mean tumor/muscle ratios in the range of 3.2-6.2 between 24 and 72 h post-injection. The kidneys and bladder were the predominant elimination organs. Gamma counting at 72 h post-injection showed 1.3-2.5% ID/g in the tumors and mean tumor/muscle ratios in the range of 4.9-9.4. CONCLUSION: 111In-C4-DTPA bound rapidly to circulating albumin upon injection and showed time-dependent uptake in the tumors demonstrating a potential for clinical application as a companion imaging diagnostic for albumin-binding anticancer drugs.

Optical and electrical properties of MoO2 and MoO3 thin films prepared from the chemically driven isothermal close space vapor transport technique.

Chemically-driven isothermal close space vapour transport was used to prepare pure MoO2 thin films which were eventually converted to MoO3 by annealing in air. According to temperature-dependent Raman measurements, the MoO2/MoO3 phase transformation was found to occur in the 225 °C-350 °C range while no other phases were detected during the transition. A clear change in composition as well as noticeable modifications of the band gap and the absorption coefficient confirmed the conversion from MoO2 to MoO3. An extensive characterization of these two pure phases was carried out. In particular, a procedure was developed to determine the dispersion relation of the refractive index of MoO2 from the shift of the interference fringes of the used SiO2/Si substrate. The obtained data of the refractive index was corrected taking into account the porosity of the samples calculated from elastic backscattering spectrometry. The Debye temperature and the residual resistivity were extracted from the electrical resistivity temperature dependence using the Bloch-Grüneisen equation. MoO3 converted samples presented a very high resistivity and a typical semiconducting behavior. They also showed intense and broad luminescence spectra composed by several contributions whose temperature behavior was examined. Furthermore, surface photovoltage spectra were taken and their relation with the photoluminescence is discussed.

High expression of CPT1b in skeletal muscle in metabolically healthy older subjects.

AIM: Ageing is often associated with metabolic abnormalities such as insulin resistance, although some people remain metabolically healthy throughout their lives. The aim of this study was to gain more insight into metabolic health with increasing age. METHODS: Two groups of robust and of frail subjects, respectively, were identified based on a composite ageing indicator and recruited from the French SU.VI.MAX 2 cohort of older disease-free subjects. In all, 14 men and 12 women, aged 67±4 years, with similar anthropometric and metabolic characteristics at baseline (BMI: 24.5±2.9kg.m-2) were included in the Compaliclamp study. Skeletal muscle biopsy was performed to assess expression of a set of metabolic and sirtuin (SIRT) genes. Also, whole-body substrate oxidation and insulin sensitivity were determined using the euglycaemic-hyperinsulinaemic clamp and indirect calorimetry techniques. RESULTS: Robust subjects were more insulin-sensitive, oxidized more lipid in a fasting state and stored more glucose during the euglycaemic - hyperinsulinaemic clamp than did frail subjects. At the gene-expression level in skeletal muscle, carnitine palmitoyltransferase 1b (CPT1b) messenger RNA (mRNA) levels were around four times higher in the robust compared with frail counterparts. Moreover, both SIRT2 and SIRT6 expression was lower in robust subjects and correlated with CPT1b expression. CONCLUSION: CPT1b overexpression could be helping to maintain metabolic health with increasing age. Thus, it is suggested that targeting CPT1b expression might be an interesting strategy to counteract frailty at an early stage. In addition, future studies should examine the role of sirtuin in CPT1b expression regulation.

A systematic literature review of observational studies of the bidirectional association between metabolic syndrome and migraine.

AIMS: To evaluate all epidemiological evidence in the literature linking the metabolic syndrome (MetS) and migraine in adults. METHODS: Database (Medline, Embase; published reports up to November 2017) and manual searches were performed. Information on data collection, sample characteristics, study design, MetS and migraine assessment, and results was extracted from each relevant publication. The methodological quality of each study was also assessed. RESULTS: A total of 15 observational epidemiological studies in adults, published between 2009 and 2017, were retrieved. Of these, one employed a prospective design, while the rest had a cross-sectional (13 studies) or case-control (one study) design. Five studies assessed the presence of migraine in individuals with MetS, whereas 10 studies assessed the presence or risk of MetS in migraineurs. Most participants were female hospital outpatients. The sole prospective cohort study reported 11-year MetS incidence of 21.8% in migraineurs with aura, 16.8% in migraineurs without aura and 14.5% in subjects without headaches. Most studies (60%) provided no statistical estimates of association. Methodological flaws included selection biases, lack of power analysis, unsuitable research plans and no multivariable analyses. Meta-analysis was not feasible with the available data. CONCLUSION: Our systematic review has identified major gaps in knowledge and weaknesses in research that should provide an impetus for future epidemiological investigations using more rigorous methodology, large general-population prospective cohorts, and substantial data on dietary behaviours and lifestyle.

Bronchopulmonary dysplasia as a risk factor for asthma in school children and adolescents: A systematic review

Background: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects extremely pre-term infants, and remains the most common complication of prematurity. Several studies have shown that prematurity predisposes to the development of asthma in school children and adolescents. Nevertheless, it is not clear to what extent a history of BPD involves an additional risk. Methods: A systematic review of studies assessing the association between BPD and asthma in school-children and adolescents was made. A literature search was carried out in the MEDLINE and EMBASE databases to retrieve articles published between 1 January 2000 and 31 August 2016. Results: A total of 17 studies comprising 7433 patients were included in the review. There was considerable heterogeneity in the definitions of BPD and asthma among studies. Overall, the prevalence of asthma was higher in children and adolescents with a history of prematurity and BPD compared with those who did not develop BPD. However, in only one of the studies did this difference reach statistical significance. The main limitation of this review was potential bias due to the lack of adjustment for confounding factors between exposure (BPD) and outcome (asthma) in most of the studies. Conclusion:Based on the studies reviewed, it cannot be argued that BPD, as an independent factor of prematurity, increases the risk of asthma defined by clinical parameters in school-children and adolescents. Further studies of greater methodological quality and homogeneous diagnostic criteria of BPD and asthma are needed for improved assessment of this association (AU)

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The BET bromodomain inhibitor CPI203 overcomes resistance to ABT-199 (venetoclax) by downregulation of BFL-1/A1 in in vitro and in vivo models of MYC+/BCL2+ double hit lymphoma.

High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, mostly known as double-hit lymphoma (DHL), is a rare entity characterized by morphologic and molecular features between Burkitt lymphoma and the clinically manageable diffuse large B-cell lymphoma (DLBCL). DHL patients usually undergo a rapidly progressing clinical course associated with resistance to standard chemo-immunotherapy. As a consequence, the prognosis of this entity is particularly poor with a median overall survival inferior to 1 year. ABT-199 (venetoclax) is a potent and selective small-molecule antagonist of BCL-2 recently approved for the treatment of a specific subtype of lymphoid neoplasm. In this study, we demonstrate that single-agent ABT-199 efficiently displaces BAX from BCL-2 complexes but fails to maintain a significant antitumor activity over time in most MYC+/BCL2+DHL cell lines and primary cultures, as well as in a xenograft mouse model of the disease. We further identify the accumulation of the BCL2-like protein BFL-1 to be a major mechanism involved in acquired resistance to ABT-199. Noteworthy, this phenomenon can be counteracted by the BET bromodomain inhibitor CPI203, since gene expression profiling identifies BCL2A1, the BFL-1 coding gene, as one of the top apoptosis-related gene modulated by this compound. Upon CPI203 treatment, simultaneous downregulation of MYC and BFL-1 further overcomes resistance to ABT-199 both in vitro and in vivo, engaging synergistic caspase-mediated apoptosis in DHL cultures and tumor xenografts. Together, these findings highlight the relevance of BFL-1 in DH lymphoma-associated drug resistance and support the combined use of a BCL-2 antagonist and a BET inhibitor as a promising therapeutic strategy for patients with aggressive DHL.

Total and specific dietary polyphenol intakes and 6-year anthropometric changes in a middle-aged general population cohort.

BACKGROUND: Dietary polyphenols are suggested antiobesogenic agents. Prospective evidence in general population of an association between polyphenol intakes and anthropometry is lacking. OBJECTIVE: To assess the associations between dietary polyphenol intakes and changes in body mass index (BMI) and waist circumference (WC) over a 6-year period. METHODS: Individual intakes of 264 different polyphenols (mg day-1) were estimated using the Phenol-Explorer database and the mean of 6-17 24-h dietary records collected in 1994-1996. BMI in kg m-2 and WC in cm were measured in 1995-1996, 1998-1999 and 2001-2002. Linear mixed-effect models allowed for the assessment of longitudinal associations between energy-adjusted quartiles of total polyphenol intake as well as intake of 15 polyphenol classes and changes of these respective polyphenol classes in anthropometry over the 6 years of follow-up. Adjustment variables included sex, age, socio-economic status, lifestyle, dietary intakes and health status. RESULTS: Participants in the highest quartile of intake of flavanones (BMI change: -0.28 (-0.43; -0.13), P=0.009), flavones (BMI change: -0.29 (-0.44; -0.14), P=0.008) and lignans (BMI change: -0.28 (-1.63; -0.09), P=0.01) experienced a less notable increase in BMI over time compared with their counterparts in the bottom quartile of intake of the respective polyphenol classes. Participants in the highest quartile of intake of flavanones (WC change: -1.39 (-2.02; -0.92), P=0.001), flavones (WC change: -1.57 (-2.32; -0.92), P=0.001), hydroxycinnamic acids (WC change: -1.27 (-1.92; -0.63), P=0.01), lignans (WC change: -1.16 (-1.80; -0.51), P=0.006) and total polyphenol intake (WC change: -1.39 (-2.05; -0.74), P=0.001) experienced a less notable increase in WC over time compared with their counterparts in the bottom quartile of intake of the respective polyphenols. CONCLUSIONS: Dietary polyphenol intakes may help reduce weight gain over time in the general population. This could have important public health implications because moderate increases in BMI and WC over time have been shown to increase disease risk.

Bronchopulmonary dysplasia as a risk factor for asthma in school children and adolescents: A systematic review.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects extremely pre-term infants, and remains the most common complication of prematurity. Several studies have shown that prematurity predisposes to the development of asthma in school children and adolescents. Nevertheless, it is not clear to what extent a history of BPD involves an additional risk. METHODS: A systematic review of studies assessing the association between BPD and asthma in school-children and adolescents was made. A literature search was carried out in the MEDLINE and EMBASE databases to retrieve articles published between 1 January 2000 and 31 August 2016. RESULTS: A total of 17 studies comprising 7433 patients were included in the review. There was considerable heterogeneity in the definitions of BPD and asthma among studies. Overall, the prevalence of asthma was higher in children and adolescents with a history of prematurity and BPD compared with those who did not develop BPD. However, in only one of the studies did this difference reach statistical significance. The main limitation of this review was potential bias due to the lack of adjustment for confounding factors between exposure (BPD) and outcome (asthma) in most of the studies. CONCLUSION: Based on the studies reviewed, it cannot be argued that BPD, as an independent factor of prematurity, increases the risk of asthma defined by clinical parameters in school-children and adolescents. Further studies of greater methodological quality and homogeneous diagnostic criteria of BPD and asthma are needed for improved assessment of this association.

Dyslipidemia as a Potential Moderator of the Association between Hearing Loss and Depressive Symptoms.

OBJECTIVES: Knowledge about moderation of the association between hearing loss and depression is scant. We investigated dyslipidemia as a potential moderator of the association between hearing/hearing loss and depressive symptoms. DESIGN: Cross-sectional study. SETTING: General population-based cohort in France (SU.VI.MAX 2; 2007-2009). PARTICIPANTS: N= 4,307 adults (mean age = 61.5 ± 6.1 y; 59.6% women). MEASUREMENTS: A score ≥ 16 on the Center for Epidemiologic Studies Depression Scale defined presence of depressive symptoms. Mean hearing level for each ear was defined as the pure-tone average of the following thresholds: 0.5, 1.0, 2.0 and 4.0 kHz; the value for the better hearing ear was retained for analysis. Hearing loss was defined as inability to hear at thresholds ≥ 25 dB in both ears. A subjective measure of perceived hearing loss was also used. Serum triglyceride, total-, LDL- and HDL-cholesterol concentrations were assessed in fasting blood samples and established cutoffs were used in multivariable logistic regression models. The interaction between hearing/hearing loss (independent variables) and each of the four lipid parameters was tested. RESULTS: Even though the interaction tests regarding LDL-, HDL- cholesterol, and triglyceride status were statistically significant, the subgroup analyses revealed few significant and somewhat unexpected findings. In fact, among individuals with low LDL-cholesterol, unlike their counterparts with high LDL-cholesterol, there was an inverse association between hearing level in the better hearing ear and depressive symptoms (OR= 0.94; 95% CI: 0.89-0.99). Regarding the subjective measure of hearing, a few of the dyslipidemia-moderated associations were statistically significant, albeit not all in the predicted direction. CONCLUSIONS: The findings provide some support for moderation of the association between hearing/hearing loss and depressive symptoms by dyslipidemia, with important lipid-specific and hearing measure-specific differences. The results could serve as impetus for future investigations in order to identify and target population subgroups with increased vulnerability to depression in the context of both sensory disability and aging.

Activity of the novel BCR kinase inhibitor IQS019 in preclinical models of B-cell non-Hodgkin lymphoma.

BACKGROUND: Pharmacological inhibition of B cell receptor (BCR) signaling has recently emerged as an effective approach in a wide range of B lymphoid neoplasms. However, despite promising clinical activity of the first Bruton's kinase (Btk) and spleen tyrosine kinase (Syk) inhibitors, a small fraction of patients tend to develop progressive disease after initial response to these agents. METHODS: We evaluated the antitumor activity of IQS019, a new BCR kinase inhibitor with increased affinity for Btk, Syk, and Lck/Yes novel tyrosine kinase (Lyn), in a set of 34 B lymphoid cell lines and primary cultures, including samples with acquired resistance to the first-in-class Btk inhibitor ibrutinib. Safety and efficacy of the compound were then evaluated in two xenograft mouse models of B cell lymphoma. RESULTS: IQS019 simultaneously engaged a rapid and dose-dependent de-phosphorylation of both constitutive and IgM-activated Syk, Lyn, and Btk, leading to impaired cell proliferation, reduced CXCL12-dependent cell migration, and induction of caspase-dependent apoptosis. Accordingly, B cell lymphoma-bearing mice receiving IQS019 presented a reduced tumor outgrowth characterized by a decreased mitotic index and a lower infiltration of malignant cells in the spleen, in tight correlation with downregulation of phospho-Syk, phospho-Lyn, and phospho-Btk. More interestingly, IQS019 showed improved efficacy in vitro and in vivo when compared to the first-in-class Btk inhibitor ibrutinib, and was active in cells with acquired resistance to this latest. CONCLUSIONS: These results define IQS019 as a potential drug candidate for a variety of B lymphoid neoplasms, including cases with acquired resistance to current BCR-targeting therapies.

Educación prenatal e inicio de la lactancia materna: Revisión de la literatura / Prenatal education and the commencement of breastfeeding: A literature review / Educação pré-natal e início do aleitamento materno: revisão da literatura

Introducción: Las recomendaciones universales para la alimentación infantil incluyen la lactancia materna (LM) exclusiva durante los primeros 6 meses de vida y posteriormente alimentación complementaria hasta los 2 años, así como la importancia del inicio de la lactancia en la primera hora de vida. Metodología: Búsqueda sistemática en diversas bases de datos del área de la salud cuyo objetivo fue determinar la influencia de la educación prenatal impartida, en general por los profesionales de la salud y en particular por la matrona, en la decisión de optar por la LM. Resultados y discusión: El éxito de la LM depende de la información y del apoyo proporcionado a la familia. Influye negativamente en su instauración y mantenimiento la falta de información y apoyo, las prácticas sanitarias inadecuadas y la escasa formación de los profesionales. Contribuye positivamente haber sido atendida por una matrona durante el embarazo. Existe evidencia, con categoría A, de que las clases prenatales realizadas por matronas aumentan la prevalencia, la duración y la exclusividad de la lactancia, así como el establecimiento de la lactancia al alta hospitalaria tras el parto. Se recomienda, con un grado B, proporcionar a los padres información sobre lactancia en las clases prenatales. No hay diferencias significativas en cuanto a los motivos por los cuales se abandona la lactancia entre las mujeres que realizaron educación prenatal con las que no la realizaron. Conclusiones: La educación maternal realizada por matronas desde la primera visita prenatal es un factor protector en el inicio y mantenimiento de la LM y debe incluir explicaciones sobre los beneficios que comporta y guías sencillas para resolver dudas y complicaciones.

Introduction: The recommendations on child nourishment include starting maternal breastfeeding within the first hour of life, and continuing it, exclusively, during the first 6 months of life; thereafter, a complementary diet can be included. Methodology: A systematic search in diverse databases related to the health area was conducted with the objective of determining the influence of prenatal education provided, in general by the health professionals, and in particular by midwives, on the mothers' decision to breastfeed. Results and discussion: The success of maternal breastfeeding depends on the information and the support provided to her family. Barriers to breastfeeding include the lack of information and support, the inadequate sanitary practices, and the poor preparation of the health professionals. Promoters to breastfeeding include having been assisted by a midwife during the partum. There is category-A evidence, that prenatal classes given by midwives, and the early establishment of maternal breastfeeding -following the partum- both increment the prevalence, duration, and exclusivity of breastfeeding. There were no significant differences related to the motives of abandoning breastfeeding among women who had prenatal education and who did not. Conclusions: The maternal education provided by midwives from the first prenatal visit is a promoting factor to establishing and maintaining breastfeeding. In general, prenatal education should include explanations of the benefits of breastfeeding, as well as simple guidelines related to the possible doubts.

Introdução: As recomendações universais para a alimentação infantil incluem o aleitamento materno (AM) exclusivo durante os primeiros 6 meses de vida e posteriormente alimentação complementar até os dois anos, assim como a importância do início do aleitamento na primeira hora de vida. Metodologia: Busca sistemática em diversas bases de dados da área de saúde, cujo objetivo foi determinar a influência da educação pré-natal ensinada, en geral pelos profissionais da saúde e em particular pela parteira, na decisão de optar pelo AM. Resultados e discussão: O sucesso do AM depende da informação e o apoio proporcionado à família. Influi negativamente em sua instauração e na manutenção pela falta de informação e apoio, as práticas sanitárias inadequadas e a escassa formação dos profissionais. Influi positivamente ter sido atendida por uma parteira durante a gravidez. Existe evidência, com categoria A, de que as aulas pré-natais realizadas por parteiras aumentam a prevalência, duração e exclusividade do aleitamento. Assim como o estabelecimento do aleitamento após a alta hospitalar trás o parto. Recomenda-se, com um grau B, proporcionar aos pais informação sobre aleitamento nas aulas pré-natais. Não há diferenças significativas quanto aos motivos pelos quais se abandona o aleitamento entre as mulheres que realizaram educação pré-natal com as que não. Conclusões: A educação materna realizada por parteiras desde a primeira visita pré-natal é um fator protetor no início e de manutenção do AM e deve incluir explicações sobre os benefícios que proporciona e guias simples para resolver dúvidas e complicações.

Consumption of Dairy Products and Cognitive Functioning: Findings from the SU.VI.MAX 2 Study.

OBJECTIVES: Research concerning the link between dairy product intake and cognition is scant while experimental studies suggest links through various biological mechanisms. This study's objective was to examine the cross-time associations of total and specific dairy product consumption with cognitive performance in aging adults. We also explored compliance with dairy intake recommendations in France. DESIGN: The study was based on the «Supplémentation en Vitamines et Minéraux Antioxydants¼ randomized trial (SU.VI.MAX, 1994-2002) and the SU.VI.MAX 2 observational follow-up study (2007-2009). SETTING: A general-population cohort in France. PARTICIPANTS: N=3,076 participants included in both the SU.VI.MAX and SU.VI.MAX 2 studies. MEASUREMENTS: Dairy product consumption was estimated using repeated 24h records (1994-1996; mean=10 records, SD=3). Cognitive performance was assessed by neuropsychologists after an average of 13 years post-baseline via a battery of six validated tests. Mean age at the time of the cognitive function evaluation was 65.5 (SD=4.6) years. Principal component analysis revealed factors for verbal memory and working memory. Associations of energy-adjusted dairy product consumption and compliance with the respective dietary guidelines with subsequent cognitive impairment were examined using ANCOVA, providing mean differences (95% confidence intervals, CI) according to tertiles (T), adjusted for confounders including overall dietary patterns. RESULTS: Total dairy product consumption was not associated with cognitive function. However, milk intake was negatively associated with verbal memory performance: mean difference T3 versus T1= -0.99 (-1.83, -0.15). Among women, consuming more than the recommended amount of dairy was negatively associated with working memory performance: excess versus adequate = -1.52 (-2.93, -0.11). CONCLUSION: Our results indicate that dairy products consumption and especially compliance with dietary guidelines regarding dairy product intake are differentially associated with performance in specific cognitive domains after a comprehensive adjustment for lifestyle factors, health status markers and dietary patterns. Further longitudinal research is needed given the limited data available.

Determining the association between types of sedentary behaviours and cardiometabolic risk factors: A 6-year longitudinal study of French adults.

AIM: This study identified the longitudinal associations between leisure-time sedentary behaviours [television (TV) viewing, computer use and reading (h/week)] and cardiometabolic risk factors, including the metabolic syndrome. METHODS: A total of 2517 participants (mean±SD age: 55.5±4.9 years) were assessed in 2001 and in 2007 for physical activity and leisure-time sedentary behaviours, anthropometry, body composition, blood pressure, fasting blood glucose and lipids, using standardized methods. Multivariate generalized linear (beta, 95% CI and P values) and logistic (OR and 95% CI) regression models were used to assess cross-sectional associations between sedentary behaviours and cardiometabolic risk factors, while a 6-year longitudinal study explored these associations as well as the odds of developing the metabolic syndrome, as defined by the NCEP ATPIII. RESULTS: Increased TV viewing time over the follow-up period was positively associated with increases in body mass index (BMI; P<0.01) and percent body fat (P<0.001), and marginally with waist circumference (P=0.06). Reverse associations were also found, with changes in BMI, percent fat mass and waist circumference positively associated with TV viewing and computer use. Associations between reading and cardiometabolic risk factors were less consistent. Each 1-h/week increase in baseline TV viewing and in reading was associated with an increase in the chances of developing the metabolic syndrome (OR=1.031, 95% CI: 0.998-1.060, P=0.07; and OR=1.032, 95% CI: 1.002-1.065, P=0.02; respectively). CONCLUSION: The present study data emphasizes the notion of differential associations of specific sedentary behaviours with cardiometabolic risk factors. They are also evidence that different longitudinal associations should be taken into account when designing public health objectives of interventions aimed at improving cardiometabolic health.

Prospective association between the dietary inflammatory index and metabolic syndrome: findings from the SU.VI.MAX study.

BACKGROUND AND AIMS: The prevention of the metabolic syndrome (MetS) is of major concern and nutrition has been shown to modulate at least partly MetS risk. Our objective was to investigate whether a pro-inflammatory diet was associated with a higher risk of MetS and its components in a large cohort of French adults. METHODS AND RESULTS: A total of 3726 participants from the Supplémentation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) cohort were included in this study. The MetS status was identified at baseline and after 13 years of follow-up using self-reported medication, data from clinical investigations and biological measurements. The dietary inflammatory index (DII) was computed using repeated 24 h-dietary records (n = 10.1 ± 3.1). Logistic and linear regression analyses were conducted to assess the prospective association of the DII (as Q, quartiles) with the incidence of MetS and with the traits contributing to the MetS-definition (blood pressure, glycaemia, triglycerides, HDL-cholesterol, waist circumference). A diet with pro-inflammatory properties, as expressed by higher DII scores, was significantly associated with a higher risk of developing the MetS (OR comparing Q4 to Q1: 1.39, 95% confidence interval 1.01-1.92, P = 0.047). Moreover, higher DII scores were associated with higher systolic and diastolic blood pressure (Ptrend across quartiles = 0.03 and 0.05, respectively) and triglycerides (Ptrend = 0.01), and with lower HDL-cholesterol (Ptrend = 0.03). CONCLUSION: A higher DII score was prospectively associated with a higher risk of MetS, with associations with blood pressure, triglycerides and HDL-cholesterol. Promotion of a healthy diet exhibiting anti-inflammatory properties may contribute to prevent cardio-metabolic disorders.

Overall and abdominal adiposity in midlife and subsequent cognitive function.

OBJECTIVES: The scientific literature supports a link between midlife adiposity and cognitive function or decline but most studies to-date have investigated only overall adiposity, often omitting important confounders from the analyses. We investigated in a cross-time design the relationships between two different midlife adiposity markers and subsequent cognitive function, testing midlife dietary patterns as a potential confounder of the associations. DESIGN: The study was based on the «Supplémentation en Vitamines et Minéraux Antioxydants¼ randomized trial (SU.VI.MAX, 1994-2002) and the SU.VI.MAX 2 observational follow-up study (2007-2009). SETTING: A general-population cohort in France. PARTICIPANTS: N=2,817 individuals (1,493 men and 1,324 women) included in both the SU.VI.MAX and SU.VI.MAX 2 studies. MEASUREMENTS: The cognitive performance of 2,817 middle-aged adults participating in the SU.VI.MAX (Supplémentation en Vitamines et Minéraux Antioxydant) study was assessed in 2007-2009 using 6 neuropsychological tests. Principal component analysis was used to derive specific cognitive scores. A composite cognitive score was also computed. Body mass index (BMI) and waist circumference (WC) were measured 13 years earlier (1994). Associations between midlife adiposity and cognitive functioning were estimated through covariance analyses. RESULTS: After adjustment for obesity-related cardio-metabolic parameters, higher BMI and larger WC at midlife predicted lower executive function. For example, the adjusted mean difference (95% confidence interval) for 1 SD increase in WC was -0.48 (-0.97, 0.00). Obese participants in midlife showed an adjusted mean difference (95% confidence interval) of -1.68 (-3.15, -0.22) compared with non-obese. Further adjustment for midlife dietary patterns slightly attenuated these associations. No relationships were observed with verbal memory or global cognitive function. CONCLUSION: Midlife overall and abdominal adiposity were similarly associated with lower executive functioning scores. Dietary patterns may partly explain such a relationship, arguing for the importance of controlling for lifestyle confounders in future studies.

The γ-secretase inhibitor PF-03084014 combined with fludarabine antagonizes migration, invasion and angiogenesis in NOTCH1-mutated CLL cells.

Targeting Notch signaling has emerged as a promising therapeutic strategy for chronic lymphocytic leukemia (CLL), especially for the poor prognostic subgroup of NOTCH1-mutated patients. Here, we report that the γ-secretase inhibitor PF-03084014 inhibits the constitutive Notch activation and induces selective apoptosis in CLL cells carrying NOTCH1 mutations. Combination of PF-03084014 with fludarabine has a synergistic antileukemic effect in primary NOTCH1-mutated CLL cells, even in the presence of the protective stroma. At transcriptional level, PF-03084014 plus fludarabine treatment induces the upregulation of the proapoptotic gene HRK and the downmodulation of MMP9, IL32 and RAC2 genes that are related to invasion and chemotaxis. PF-03084014 also overcomes fludarabine-mediated activation of nuclear factor-κB signaling. Moreover, this combination impairs angiogenesis and CXCL12-induced responses in NOTCH1-mutated CLL cells, in particular those related to tumoral migration and invasion. Importantly, all these collaborative effects are specific for NOTCH1 mutation and do not occur in unmutated cases. In conclusion, we provide evidence that Notch is a therapeutic target in CLL cases with NOTCH1-activating mutations, supporting the use of Notch pathway inhibitors in combination with chemotherapy as a promising approach for the treatment of these high-risk CLL patients.

Blood pressure variability: cardiovascular risk integrator or independent risk factor?

Blood pressure (BP) variability is associated with several cardiovascular (CV) risk factors. Is BP variability measurement of any additive value, in terms of CV risk assessment strategies? To answer this question, we analyzed data from the SU.FOL.OM3 secondary prevention trial that included 2501 patients with background of CV disease history (coronary or cerebrovascular disease). BP was measured every year allowing calculation of variability of BP, expressed as s.d. and coefficient of variability (s.d./mean systolic BP) in 2157 patients. We found that systolic BP variability was associated with several CV risk factors: principally hypertension, age, and diabetes. Furthermore, all antihypertensives were positively associated with variability. Logistic regression analysis revealed that three factors were independent predictors of major CV event: coefficient of variability of systolic BP (OR=1.23 per s.d., 95% CI: 1.04-1.46, P=0.016), current smoking (OR=1.94, 95% CI: 1.03-3.66, P=0.039), and inclusion for cerebrovascular disease (OR=1.92, 95% CI: 1.29-2.87, P=0.001). Finally, when comparing logistic regression models characteristics without, and then with, inclusion of BP variability, there was a modest but statistically significant improvement (P=0.04). In conclusion, age, BP and diabetes were the major determinants of BP variability. Furthermore, BP variability has an independent prognostic value in the prediction of major CV events; but improvement in the prediction model was quite modest. This last finding is more in favor of BP variability acting as an integrator of CV risk than acting as a robust independent CV risk factor in this high-risk population.