Transitions between Mild Cognitive Impairment, Dementia, and Mortality:The Importance of Olfaction

BackgroundThe existing literature suggests that impaired olfaction may be an early marker for cognitive decline. Tracking the earliest stages of the progression to dementia is paramount, and yet the importance of olfactory ability throughout cognitive states and death remains unclear.MethodsDrawing data from the Rush Memory and Aging Project (N = 1 501; 74% female), olfactory ability was assessed using the Brief Smell Identification Test (range = 0-16), while cognitive states (unimpaired, mild cognitive impairment [MCI], and dementia) were determined using a 3-step neuropsychological diagnostic protocol at up to 15 annual occasions. Multistate survival models simultaneously estimated the association of olfactory ability on transitions through cognitive states and death, while multinomial regression models estimated cognitively unimpaired and total life expectancies.ResultsHigher olfactory scores were associated with a reduced risk of transitioning from unimpaired cognition to MCI (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.82-0.88) and from MCI to dementia (HR = 0.89, 95% CI = 0.86-0.93), indicating that 1-unit increase in olfactory scores was associated with an approximate 14% and 11% reduction in risk, respectively. Additionally, higher olfactory scores were associated with a greater likelihood of transitioning backward from MCI to unimpaired cognition (HR = 1.07, 95% CI = 1.02-1.12). Furthermore, higher baseline olfactory scores were associated with more years of longevity without cognitive impairment. However, olfaction was not associated with the transition to death when accounting for transitions through cognitive states.ConclusionsFindings suggest that higher olfactory identification scores are associated with a decreased risk of transitioning to impaired cognitive states and that associations between olfaction and mortality may occur primarily through the pathway of neurodegeneration

PGC-1α induced browning promotes involution and inhibits lactation in mammary glands

The PPARγ coactivator 1α (PGC-1α) is a transcriptional regulator of mitochondrial biogenesis and oxidative metabolism. Recent studies have highlighted a fundamental role of PGC-1α in promoting breast cancer progression and metastasis, but the physiological role of this coactivator in the development of mammary glands is still unknown. First, we show that PGC-1α is highly expressed during puberty and involution, but nearly disappeared in pregnancy and lactation. Then, taking advantage of a newly generated transgenic mouse model with a stable and specific overexpression of PGC-1α in mammary glands, we demonstrate that the re-expression of this coactivator during the lactation stage leads to a precocious regression of the mammary glands. Thus, we propose that PGC-1α action is non-essential during pregnancy and lactation, whereas it is indispensable during involution. The rapid preadipocyte–adipocyte transition, together with an increased rate of apoptosis promotes a premature mammary glands involution that cause lactation defects and pup growth retardation. Overall, we provide new insights in the comprehension of female reproductive cycles and lactation deficiency, thus opening new roads for mothers that cannot breastfeed

Qualidade de sementes de soja submetidas a diferentes volumes de calda no tratamento de sementes, sob efeito do armazenamento.

Edição Especial contendo os Anais do XVIII Congresso Brasileiro de Sementes, Florianópolis, set. 2013

Adhesion of platelets to colon cancer cells is necessary to promote tumor development in xenograft, genetic and inflammation models

Platelets represent the linkage between tissue damage and inflammatory response with a putative role in tumorigenesis. Given the importance of the microenvironment in colon cancer development, we elucidated the eventual role of platelets‐cancer cells crosstalk in in vivo colon cancer models. To evaluate the involvement of platelets in intestinal tumorigenesis, we first analyzed if the ablation of β‐integrin P‐selectin that drives platelets‐cell adhesion, would contribute to platelets‐colon cancer cell interaction and drive cancer progression. In a xenograft tumor model, we observed that when tumors are inoculated with platelets, the ablation of P‐selectin significantly reduced tumor growth compared to control platelets. Furthermore, in genetic models, as well as in chronic colitis‐associated colorectal carcinogenesis, P‐selectin ablated mice displayed a significant reduction in tumor number and size compared to control mice. Taken together, our data highlights the importance of platelets in the tumor microenvironment for intestinal tumorigenesis. These results support the hypothesis that a strategy aimed to inhibit platelets adhesion to tumor cells are able to block tumor growth and could represent a novel therapeutic approach to colon cancer treatment

Remote multiparametric monitoring and management of heart failure patients through cardiac implantable electronic devices

In this review we focus on heart failure (HF) which, as known, is associated with a substantial risk of hospitalizations and adverse cardiovascular outcomes, including death. In recent years, systems to monitor cardiac function and patient parameters have been developed with the aim to detect subclinical pathophysiological changes that precede worsening HF. Several patient-specific parameters can be remotely monitored through cardiac implantable electronic devices (CIED) and can be combined in multiparametric scores predicting patients’ risk of worsening HF with good sensitivity and moderate specificity. Early patient management at the time of pre-clinical alerts remotely transmitted by CIEDs to physicians might prevent hospitalizations. However, it is not clear yet which is the best diagnostic pathway for HF patients after a CIED alert, which kind of medications should be changed or escalated, and in which case in-hospital visits or in-hospital admissions are required. Finally, the specific role of healthcare professionals involved in HF patient management under remote monitoring is still matter of definition. We analyzed recent data on multiparametric monitoring of patients with HF through CIEDs. We provided practical insights on how to timely manage CIED alarms with the aim to prevent worsening HF. We also discussed the role of biomarkers and thoracic echo in this context, and potential organizational models including multidisciplinary teams for remote care of HF patients with CIEDs

Controlled thermodynamics for tunable electron doping of graphene on Ir(111)

The electronic properties and surface structures of K-doped graphene supported on Ir(111) are characterized as a function of temperature and coverage by combining low-energy electron diffraction, angle-resolved photoemission spectroscopy, and density functional theory (DFT) calculations. Deposition of K on graphene at room temperature (RT) yields a stable (√3 × √3) R30° surface structure having an intrinsic electron doping that shifts the graphene Dirac point by ED = 1.30 eV below the Fermi level. Keeping the graphene substrate at 80 K during deposition generates instead a (2 × 2) phase, which is stable until full monolayer coverage. Further deposition of K followed by RT annealing develops a double-layer K-doped graphene that effectively doubles the K coverage and the related charge transfer, as well as maximizing the doping level (ED = 1.61 eV). The measured electron doping and the surface reconstructions are rationalized by DFT calculations. These indicate a large thermodynamic driving force for K intercalation below the graphene layer. The electron doping and Dirac point shifts calculated for the different structures are in agreement with the experimental measurements. In particular, the K4s bands are shown to be sensitive to both the K intercalation and periodicity and are therefore suggested as a fingerprint for the location and ordering of the K dopants

Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis

Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis (EAE). In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP) induction was favored over long-term depression (LTD) in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β) perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC) without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS

Volume de calda com diferentes produtos e seu efeito na qualidade fisiológica de sementes de soja.

O cultivo de soja de alto rendimento requer o uso de tecnologias tais como fungicidas, inseticidas, micronutrientes e inoculantes que são veiculados com as sementes. Além disso, a aplicação de biorreguladores via semente tem sido indicada por várias empresas. Esses reguladores são substâncias naturais ou sintéticas que podem ser aplicadas nas sementes com a finalidade de incrementar a produção e melhorar a qualidade das sementes. Isso resulta na aplicação de elevados volumes de calda, o que pode afetar as qualidades física e fisiológica das sementes. O objetivo do trabalho foi determinar a influência de diferentes volumes de calda via tratamento de sementes e seu efeito na qualidade fisiológica. Foram utilizadas sementes da cultivar BRS 232, de dois lotes comerciais, um com alto e o outro com vigor médio. O delineamento experimental foi o inteiramente casualizado, com tratamentos em esquema fatorial 2 níveis de vigor (alto e médio vigor) X 4 volumes de calda (0, 500, 1000 e 1500 mL kg-1). Os tratamentos 0, 500, 1000 e 1500 mL kg-1 de sementes foram representados, respectivamente, por uma testemunha, um tratamento reduzido (Fungicida + Inoculante), um tratamento completo (Fungicida + Micronutriente + Inseticida + Inoculante) e um tratamento completo + biorregulador Stimulate®. A qualidade sementes foi avaliada pelos testes de germinação (primeira contagem e contagem final), de envelhecimento acelerado e de comprimento de plântula. O teste F foi conclusivo na comparação das médias dos efeitos dos níveis de vigor. Concluiu-se que, em lotes de alto e médio vigor, é possível utilizar o tratamento completo com o biorregulador Stimulate®, com elevado volume de calda (1500 mL kg-1), sem que ocorram danos fisiológico à semente de soja