Whether consumption of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) is associated with risk of mortality is of public health interest.
We examined associations between ...consumption of SSBs and ASBs with risk of total and cause-specific mortality among 37 716 men from the Health Professional's Follow-up study (from 1986 to 2014) and 80 647 women from the Nurses' Health study (from 1980 to 2014) who were free from chronic diseases at baseline. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals.
We documented 36 436 deaths (7896 cardiovascular disease CVD and 12 380 cancer deaths) during 3 415 564 person-years of follow-up. After adjusting for major diet and lifestyle factors, consumption of SSBs was associated with a higher risk of total mortality; pooled hazard ratios (95% confidence intervals) across categories (<1/mo, 1-4/mo, 2-6/week, 1-<2/d, and ≥2/d) were 1.00 (reference), 1.01 (0.98, 1.04), 1.06 (1.03, 1.09), 1.14 (1.09, 1.19), and 1.21 (1.13, 1.28; P trend <0.0001). The association was observed for CVD mortality (hazard ratio comparing extreme categories was 1.31 95% confidence interval, 1.15, 1.50, P trend <0.0001) and cancer mortality (1.16 1.04, 1.29, P trend =0.0004). ASBs were associated with total and CVD mortality in the highest intake category only; pooled hazard ratios (95% confidence interval) across categories were 1.00 (reference), 0.96 (0.93, 0.99), 0.97 (0.95, 1.00), 0.98 (0.94, 1.03), and 1.04 (1.02, 1.12; P trend = 0.01) for total mortality and 1.00 (reference), 0.93 (0.87, 1.00), 0.95 (0.89, 1.00), 1.02 (0.94, 1.12), and 1.13 (1.02, 1.25; P trend = 0.02) for CVD mortality. In cohort-specific analysis, ASBs were associated with mortality in NHS (Nurses' Health Study) but not in HPFS (Health Professionals Follow-up Study) ( P interaction, 0.01). ASBs were not associated with cancer mortality in either cohort.
Consumption of SSBs was positively associated with mortality primarily through CVD mortality and showed a graded association with dose. The positive association between high intake levels of ASBs and total and CVD mortality observed among women requires further confirmation.
Centromeres are chromosomal elements that are both necessary and sufficient for chromosome segregation. However, the puzzlingly broad range in centromere complexity, from simple “point” centromeres ...to multi-megabase arrays of DNA satellites, has defied explanation. We posit that ancestral centromeres were epigenetically defined and that point centromeres, such as those of budding yeast, have derived from the partitioning elements of selfish plasmids. We further propose that the larger centromere sizes in plants and animals and the rapid evolution of their centromeric proteins is the result of an intense battle for evolutionary dominance due to the asymmetric retention of only one product of female meiosis.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus 2019 (COVID-19) pneumonia. Little is known about the kinetics, tissue distribution, ...cross-reactivity, and neutralization antibody response in patients with COVID-19. Two groups of patients with RT-PCR-confirmed COVID-19 were enrolled in this study: 12 severely ill patients in intensive care units who needed mechanical ventilation and 11 mildly ill patients in isolation wards. Serial clinical samples were collected for laboratory detection. Results showed that most of the severely ill patients had viral shedding in a variety of tissues for 20-40 days after onset of disease (8/12, 66.7%), while the majority of mildly ill patients had viral shedding restricted to the respiratory tract and had no detectable virus RNA 10 days after onset (9/11, 81.8%). Mildly ill patients showed significantly lower IgM response compared with that of the severe group. IgG responses were detected in most patients in both the severe and mild groups at 9 days after onset, and remained at a high level throughout the study. Antibodies cross-reactive to SARS-CoV and SARS-CoV-2 were detected in patients with COVID-19 but not in patients with MERS. High levels of neutralizing antibodies were induced after about 10 days after onset in both severely and mildly ill patients which were higher in the severe group. SARS-CoV-2 pseudotype neutralization test and focus reduction neutralization test with authentic virus showed consistent results. Sera from patients with COVID-19 inhibited SARS-CoV-2 entry. Sera from convalescent patients with SARS or Middle East respiratory syndrome (MERS) did not. Anti-SARS-CoV-2 S and N IgG levels exhibited a moderate correlation with neutralization titers in patients' plasma. This study improves our understanding of immune response in humans after SARS-CoV-2 infection.
A growing number of cohort studies suggest a potential role of dairy consumption in type 2 diabetes (T2D) prevention. The strength of this association and the amount of dairy needed is not clear.
We ...performed a meta-analysis to quantify the associations of incident T2D with dairy foods at different levels of intake.
A systematic literature search of the PubMed, Scopus, and Embase databases (from inception to 14 April 2015) was supplemented by hand searches of reference lists and correspondence with authors of prior studies. Included were prospective cohort studies that examined the association between dairy and incident T2D in healthy adults. Data were extracted with the use of a predefined protocol, with double data-entry and study quality assessments. Random-effects meta-analyses with summarized dose-response data were performed for total, low-fat, and high-fat dairy, (types of) milk, (types of) fermented dairy, cream, ice cream, and sherbet. Nonlinear associations were investigated, with data modeled with the use of spline knots and visualized via spaghetti plots.
The analysis included 22 cohort studies comprised of 579,832 individuals and 43,118 T2D cases. Total dairy was inversely associated with T2D risk (RR: 0.97 per 200-g/d increment; 95% CI: 0.95, 1.00;P= 0.04;I(2)= 66%), with a suggestive but similar linear inverse association noted for low-fat dairy (RR: 0.96 per 200 g/d; 95% CI: 0.92, 1.00;P= 0.072;I(2)= 68%). Nonlinear inverse associations were found for yogurt intake (at 80 g/d, RR: 0.86 compared with 0 g/d; 95% CI: 0.83, 0.90;P< 0.001;I(2)= 73%) and ice cream intake (at ∼10 g/d, RR: 0.81; 95% CI: 0.78, 0.85;P< 0.001;I(2)= 86%), but no added incremental benefits were found at a higher intake. Other dairy types were not associated with T2D risk.
This dose-response meta-analysis of observational studies suggests a possible role for dairy foods, particularly yogurt, in the prevention of T2D. Results should be considered in the context of the observed heterogeneity.
To review the contribution of the Nurses' Health Studies (NHS and NHS II) in addressing hypotheses regarding risk factors for and consequences of obesity.
Narrative review of the publications of the ...NHS and NHS II between 1976 and 2016.
Long-term NHS research has shown that weight gain and being overweight or obese are important risk factors for type 2 diabetes, cardiovascular diseases, certain types of cancers, and premature death. The cohorts have elucidated the role of dietary and lifestyle factors in obesity, especially sugar-sweetened beverages, poor diet quality, physical inactivity, prolonged screen time, short sleep duration or shift work, and built environment characteristics. Genome-wide association and gene-lifestyle interaction studies have shown that genetic factors predispose individuals to obesity but that such susceptibility can be attenuated by healthy lifestyle choices. This research has contributed to evolving clinical and public health guidelines on the importance of limiting weight gain through healthy dietary and lifestyle behaviors.
The NHS cohorts have contributed to our understanding of the risk factors for and consequences of obesity and made a lasting impact on clinical and public health guidelines on obesity prevention.
Abstract A recently emerged novel influenza A H1N1 virus continues to spread globally. The virus contains a novel constellation of gene segments, the nearest known precursors being viruses found in ...swine and it likely arose through reassortment of two or more viruses of swine origin. H1N1, H1N2 and H3N2 subtype swine influenza viruses have occasionally infected humans before but such zoonotic transmission events did not lead to sustained human-to-human transmission in the manner this swine-origin influenza virus (S-OIV) has done. Its transmission among humans appears to be higher than that observed with seasonal influenza. Children and young adults appear to those most affected and also those who appear to maintain transmission. Clinical disease generally appears mild but complications leading to hospitalization can occur, especially in those with underlying lung or cardiac disease, diabetes or those on immunosuppresive therapies. There are concerns that the virus may reassort with existing human influenza virus giving rise to more transmissible or more pathogenic viruses. The virus appears to retain the potential to transmit back to swine and thus continued reassortment with swine viruses is a cause for concern.
Human umbilical cord mesenchymal stromal cells are more effective than those derived from human bone marrow in alleviating mechanisms of acute lung injury induced by influenza A(H5N1) virus, such as ...impaired alveolar fluid clearance and alveolar protein permeability.
Abstract
Background
Highly pathogenic avian influenza viruses can cause severe forms of acute lung injury (ALI) in humans, where pulmonary flooding leads to respiratory failure. The therapeutic benefits of bone marrow mesenchymal stromal cells (MSCs) have been demonstrated in a model of ALI due to influenza A(H5N1) virus. However, clinical translation is impractical and limited by a decline in efficacy as the age of the donor increases. Umbilical cord MSCs (UC-MSCs) are easier to obtain by comparison, and their primitive source may offer more-potent therapeutic effects.
Methods
Here we investigate the therapeutic efficacy of UC-MSCs on the mechanisms of pulmonary edema formation and alveolar fluid clearance and protein permeability of A(H5N1)-infected human alveolar epithelial cells. UC-MSCs were also tested in a mouse model of influenza ALI.
Results
We found that UC-MSCs were effective in restoring impaired alveolar fluid clearance and protein permeability of A(H5N1)-infected human alveolar epithelial cells. UC-MSCs consistently outperformed bone marrow MSCs, partly because of greater growth factor secretion of angiopoietin 1 and hepatocyte growth factor. Conditioned UC-MSC medium and UC-MSC exosomes were also able to recapitulate these effects. However, UC-MSCs only slightly improved survival of A(H5N1)-infected mice.
Conclusions
Our results suggest that UC-MSCs are effective in restoring alveolar fluid clearance and protein permeability in A(H5N1)-associated ALI and confer functional in addition to practical advantages over conventional bone marrow MSCs.
Influenza A viruses evolve rapidly to escape host immunity, causing reinfection. The form and duration of protection after each influenza virus infection are poorly understood. We quantify the ...dynamics of protective immunity by fitting individual-level mechanistic models to longitudinal serology from children and adults. We find that most protection in children but not adults correlates with antibody titers to the hemagglutinin surface protein. Protection against circulating strains wanes to half of peak levels 3.5-7 years after infection in both age groups, and wanes faster against influenza A(H3N2) than A(H1N1)pdm09. Protection against H3N2 lasts longer in adults than in children. Our results suggest that influenza antibody responses shift focus with age from the mutable hemagglutinin head to other epitopes, consistent with the theory of original antigenic sin, and might affect protection. Imprinting, or primary infection with a subtype, has modest to no effect on the risk of non-medically attended infections in adults.
Emotion has a substantial influence on the cognitive processes in humans, including perception, attention, learning, memory, reasoning, and problem solving. Emotion has a particularly strong ...influence on attention, especially modulating the selectivity of attention as well as motivating action and behavior. This attentional and executive control is intimately linked to learning processes, as intrinsically limited attentional capacities are better focused on relevant information. Emotion also facilitates encoding and helps retrieval of information efficiently. However, the effects of emotion on learning and memory are not always univalent, as studies have reported that emotion either enhances or impairs learning and long-term memory (LTM) retention, depending on a range of factors. Recent neuroimaging findings have indicated that the amygdala and prefrontal cortex cooperate with the medial temporal lobe in an integrated manner that affords (i) the amygdala modulating memory consolidation; (ii) the prefrontal cortex mediating memory encoding and formation; and (iii) the hippocampus for successful learning and LTM retention. We also review the nested hierarchies of circular emotional control and cognitive regulation (bottom-up and top-down influences) within the brain to achieve optimal integration of emotional and cognitive processing. This review highlights a basic evolutionary approach to emotion to understand the effects of emotion on learning and memory and the functional roles played by various brain regions and their mutual interactions in relation to emotional processing. We also summarize the current state of knowledge on the impact of emotion on memory and map implications for educational settings. In addition to elucidating the memory-enhancing effects of emotion, neuroimaging findings extend our understanding of emotional influences on learning and memory processes; this knowledge may be useful for the design of effective educational curricula to provide a conducive learning environment for both traditional "live" learning in classrooms and "virtual" learning through online-based educational technologies.
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