Aqueous extract of Swietenia macrophylla leaf exerts an anti-inflammatory effect in a murine model of Parkinson's disease induced by 6-OHDA.

Introduction: Parkinson's disease affects 2% of the population aged over 65 years and is the second most common neurodegenerative disorder in the general population. The appearance of motor symptoms is associated with the degeneration of dopaminergic neurons in the nigrostriatal pathway. Clinically significant nonmotor symptoms are also important for severe disability with disease progression. Pharmacological treatment with levodopa, which involves dopamine restitution, results in a temporary improvement in motor symptoms. Among the mechanisms underlying the pathogenesis of the disease are exacerbated oxidative stress, mitochondrial dysfunction, and neuroinflammation. A phytochemical prospecting study showed that the aqueous extract of the leaves from Swietenia macrophylla (Melineaceae), known as mahogany, has polyphenols with antioxidant and anti-inflammatory capacity in a significantly higher percentage than leaf extracts from other Amazonian plants. Furthermore, the antioxidant and anti-inflammatory capacity of aqueous extract of mahogany leaf has already been demonstrated in an in vitro model. In this study, we hypothesized that the aqueous extract of mahogany leaf (AEML) has a neuroprotective effect in a murine model of Parkinson's disease induced by 6-hydroxidopamine (6-OHDA), due to antioxidant and anti-inflammatory properties of its phenolic compounds. Methods: Mice were treated daily with the mahogany extract at a dose of 50 mg/kg, starting 7 days before 6-OHDA infusion until post-surgery day 7. Results and discussion: The animals from the 6-OHDA/mahogany group, which corresponds to animals injected with the toxin and treated with aqueous extract of the mahogany leaf, presented distinct behavioral phenotypes after apomorphine challenge and were therefore subdivided into 2 groups, 6-OHDA/mahogany F1 and 6-OHDA/mahogany F2. The F1 group showed a significant increase in contralateral rotations, whereas the F2 group did not show rotations after the apomorphine stimulus. In the F1 group, there was an increase, although not significant, in motor performance in the open field and elevated plus maze tests, whereas in the F2 group, there was significant improvement, which may be related to the lesser degree of injury to the nigrostriatal dopaminergic pathway. The TH+ histopathological analysis, a dopaminergic neuron marker, confirmed that the lesion to the nigrostriatal dopaminergic pathway was more pronounced in 6-OHDA/mahogany F1 than in 6-OHDA/mahogany F2. Our main result consisted of signs of improvement in the inflammatory profile in both the F1 and F2 6-OHDA/mahogany groups, such as a lower number of IBA-1+ microglial cells in the ventral striatum and substantia nigra pars compacta and a reduction in GFAP+ expression, an astrocyte marker, in the dorsal striatum. In this study, several bioactive compounds in the aqueous extract of mahogany leaf may have contributed to the observed beneficial effects. Further studies are necessary to better characterize their applicability for treating chronic degenerative diseases with inflammatory and oxidative bases, such as Parkinson's disease.

Feasibility and effectiveness of a remote individual rehabilitation program for people with Parkinson's disease living in the Brazilian Amazon: a randomized clinical trial.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder, and the current treatment involves pharmacological intervention and physiotherapy. Telerehabilitation, which involves remote support and guidance for patients undergoing rehabilitation, can potentially improve access to physiotherapy services for people with Parkinson's disease, especially those who face geographic barriers to healthcare. The primary aim of this study was to assess the feasibility and efficacy of a telerehabilitation program for people with Parkinson's disease living in an underrepresented community of the Brazilian Amazon. We conducted a parallel-group, single-center, single-blind, phase 2 randomized controlled clinical trial involving 19 participants diagnosed with Parkinson's disease from Belém, Brazil. Participants were assigned to a 4-week individual telerehabilitation program or a booklet-based exercise program (control group). Assessments were conducted before the intervention, immediately after the intervention, and 4 weeks after the end of the intervention. We showed that our telerehabilitation program had high adherence among patients, with minimal adverse effects. Both telerehabilitation and booklet orientation reduced the time to complete the Timed Up and Go test. In conclusion, our telerehabilitation program was feasible and effective for people with Parkinson's disease in an Amazonian setting. This trial was registered at the Registro Brasileiro de Ensaios Clínicos (ReBEC) under the identifier: RBR-6sz837s.

Increased Relative Delta Bandpower and Delta Indices Revealed by Continuous qEEG Monitoring in a Rat Model of Ischemia-Reperfusion.

The present study describes the electroencephalographic changes that occur during cerebral ischemia and reperfusion in animals submitted to transient focal cerebral ischemia by middle cerebral artery occlusion (MCAO) for 30 min. For this, male Wistar rats were divided into two groups (n = 6 animals/group): (1) sham (control) group, and (2) ischemic/reperfusion group. The quantitative electroencephalography (qEEG) was recorded during the ischemic and immediate reperfusion (acute) phases, and then once a day for 7 days after the MCAO (subacute phase). The acute phase was characterized by a marked increase in the relative delta wave band power (p < 0.001), with a smaller, but significant increase in the relative alpha wave bandpower in the ischemic stroke phase, in comparison with the control group (p = 0.0054). In the immediate reperfusion phase, however, there was an increase in the theta, alpha, and beta waves bandpower (p < 0.001), but no alteration in the delta waves (p = 0.9984), in comparison with the control group. We also observed high values in the delta/theta ratio (DTR), the delta/alpha ratio (DAR), and the (delta+theta)/(alpha+beta) ratio (DTABR) indices during the ischemia (p < 0.05), with a major reduction in the reperfusion phase. In the subacute phase, the activity of all the waves was lower than that of the control group (p < 0.05), although the DTR, DAR, and DTABR indices remained relatively high. In conclusion, early and accurate identification of decreased delta wave bandpower, DTR, DAR, and DTABR indices, and an increase in the activity of other waves in the immediate reperfusion phase may represent an important advance for the recognition of the effectiveness of reperfusion therapy.

Postural adjustments impairments in elderly people with chronic low back pain.

Chronic low back pain (CLBP) is associated with postural control impairments and is highly prevalent in elderly people. The objective of this study is to verify whether anticipatory postural adjustments (APAs) and compensatory postural adjustments (CPAs) are affected by CLBP in elderly people by assessing their postural control during a self-initiated perturbation paradigm induced by rapid upper arm movement when pointing to a target. The participants' lower limb muscle onset and center of pressure (COP) displacements were assessed prior to perturbation and throughout the entire movement. T0 moment (i.e., the beginning of the movement) was defined as the anterior deltoid (DEL) onset, and all parameters were calculated with respect to it. The rectus femoris (RT), semitendinosus (ST), and soleous (SOL) showed delayed onset in the CLBP group compared with the control group: RF (control: - 0.094 ± 0.017 s; CLBP: - 0.026 ± 0.012 s, t = 12, p < 0.0001); ST (control: - 0.093 ± 0.013 s; CLBP: - 0.018 ± 0.019 s, t = 12, p < 0.0001); and SOL (control: - 0.086 ± 0.018 s; CLBP: - 0.029 ± 0.015 s, t = 8.98, p < 0.0001). In addition, COP displacement was delayed in the CLBP group (control: - 0.035 ± 0.021 s; CLBP: - 0.015 ± 0.009 s, t = 3; p = 0.003) and presented a smaller amplitude during APA COPAPA [control: 0.444 cm (0.187; 0.648); CLBP: 0.228 cm (0.096; 0.310), U = 53, p = 0.012]. The CLBP group required a longer time to reach the maximum displacement after the perturbation (control: 0.211 ± 0.047 s; CLBP 0.296 ± 0.078 s, t = 3.582, p = 0.0013). This indicates that CLBP elderly patients have impairments to recover their postural control and less efficient anticipatory adjustments during the compensatory phase. Our results suggest that people with CLBP have altered feedforward hip and ankle muscle control, as shown from the SOL, ST, and RT muscle onset. This study is the first study in the field of aging that investigates the postural adjustments of an elderly population with CLBP. Clinical assessment of this population should consider postural stability as part of a rehabilitation program.

The Gut and Parkinson's Disease-A Bidirectional Pathway.

Humans evolved a symbiotic relationship with their gut microbiome, a complex microbial community composed of bacteria, archaea, protists, and viruses, including bacteriophages. The enteric nervous system (ENS) is a gateway for the bidirectional communication between the brain and the gut, mostly through the vagus nerve (VN). Environmental exposure plays a pivotal role in both the composition and functionality of the gut microbiome and may contribute to susceptibility to neurodegenerative disorders, such as Parkinson's disease (PD). The neuropathological hallmark of PD is the widespread appearance of alpha-synuclein aggregates in both the central and peripheral nervous systems, including the ENS. Many studies suggest that gut toxins can induce the formation of α-syn aggregates in the ENS, which may then be transmitted in a prion-like manner to the CNS through the VN. PD is strongly associated with aging and its negative effects on homeostatic mechanisms protecting from inflammation, oxidative stress, and protein malfunction. In this mini-review, we revisit some landmark discoveries in the field of Parkinson's research and focus on the gut-brain axis. In the process, we highlight evidence showing gut-associated dysbiosis and related microbial-derived components as important players and risk factors for PD. Therefore, the gut microbiome emerges as a potential target for protective measures aiming to prevent PD onset.

GBA mutations p.N370S and p.L444P are associated with Parkinson's disease in patients from Northern Brazil.

Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.

GBA mutations p.N370S and p. L444P are associated with Parkinson's disease in patients from Northern Brazil / Mutações p.N370S e p. L444P no gene GBA estão associadas com doença de Parkinson em pacientes do norte do Brasil

ABSTRACT Mutations of the GBA gene have been reported in patients with Parkinson's disease (PD) from a number of different countries, including Brazil. In order to confirm this pattern in a sample of PD patients from northern Brazil, we conducted a case-control study of the occurrence of the two most common mutations of the GBA gene (c.1226A>G; p.N370S and c.1448T>C; p.L444P) in a group of 81 PD patients and 81 control individuals, using PCR-RFLP, confirmed by the direct sequencing of the PCR products. In the patient group, three patients (3.7%) were heterozygous for the GBA c.1226A>G; p.N370S mutation, and three (3.7%) for GBA c.1448T>C; p.L444P Neither mutation was detected in the control group (p =0.0284). Patients with the c.1448T>C; p.L444P mutation showed a tendency to have an earlier disease onset, but a larger sample number is required to confirm this observation. Our results suggest an association between the GBA c.1226A>G; p.N370S and c.1448T>C; p.L444P mutations and the development of PD in the population of patients from the Northern Brazil.

RESUMO Mutações no gene GBA têm sido reportadas em pacientes com doença de Parkinson (DP) em diferentes países, incluindo o Brasil. Com o objetivo de confirmar esse padrão em uma amostra de pacientes com DP provenientes do Norte brasileiro, foi conduzindo esse estudo caso-controle investigando a frequência das duas mutações mais comuns do gene GBA (c.1226A>G; p.N370S e c.1448T>C; p.L444P) em um grupo de 81 pacientes com DP e 81 controles, usando PCR-RFLP e confirmado pelo sequenciamento direto de produtos de PCR. No grupo experimental, três pacientes (3,7%) foram heterozigotos para a mutação c.1226A>G; p.N370S e três (3,7%), para a mutação c.1448T>C; p.L444P Nenhuma das duas mutações foi detectada no grupo controle (p =0,0284). Pacientes com a mutação c.1448T>C; p.L444P demonstraram uma tendência a apresentar os sintomas mais precocemente, porém um número amostrai maior é necessário para confirmar essa observação. Nossos resultados sugerem uma associação entre essas duas mutações no gene GBA e o desenvolvimento de DP na população de pacientes do norte Brasileiro.

Global miRNA expression profile reveals novel molecular players in aneurysmal subarachnoid haemorrhage.

The molecular mechanisms behind aneurysmal subarachnoid haemorrhage (aSAH) are still poorly understood. Expression patterns of miRNAs may help elucidate the post-transcriptional gene expression in aSAH. Here, we evaluate the global miRNAs expression profile (miRnome) of patients with aSAH to identify potential biomarkers. We collected 33 peripheral blood samples (27 patients with cerebral aneurysm, collected 7 to 10 days after the haemorrhage, when usually is the cerebral vasospasm risk peak, and six controls). Then, were performed small RNA sequencing using an Illumina Next Generation Sequencing (NGS) platform. Differential expression analysis identified eight differentially expressed miRNAs. Among them, three were identified being up-regulated, and five down-regulated. miR-486-5p was the most abundant expressed and is associated with poor neurological admission status. In silico miRNA gene target prediction showed 148 genes associated with at least two differentially expressed miRNAs. Among these, THBS1 and VEGFA, known to be related to thrombospondin and vascular endothelial growth factor. Moreover, MYC gene was found to be regulated by four miRNAs, suggesting an important role in aneurysmal subarachnoid haemorrhage. Additionally, 15 novel miRNAs were predicted being expressed only in aSAH, suggesting possible involvement in aneurysm pathogenesis. These findings may help the identification of novel biomarkers of clinical interest.

Glycemic Variability and Insulin Needs in Patients with Type 1 Diabetes Mellitus Supplemented with Vitamin D: A Pilot Study Using Continuous Glucose Monitoring System.

BACKGROUND: Recent studies suggest that glycemic variability could influence the risk of complications in Type 1 Diabetes Mellitus (T1DM). There are no data about the action of Vitamin D (VD) on glycemic variability. Our pilot study aims to evaluate glycemic variability and insulin needs in patients with T1DM supplemented with VD. METHODS: 22 Patients received doses of 4000 and 10000 IU/day of cholecalciferol for 12 weeks, according to the patient's baseline VD levels and underwent continuous glucose monitoring system. RESULTS: Correlations were found between percentage variation (Δ) of glycemia standard deviation (ΔSDG), calculated using continuous glucose monitoring, with Δ of basal (r = 0.6; p <0.01) and total insulin dose (r = 0.6; p <0.01). Correlations between VD status after supplementation and Δ of prandial (r = 0.5; p <0.05) and total insulin dose (r = 0.4; p <0.05) were found, suggesting that the dose of insulin needed by patients is lower when VD status is better. We divided patients in two subgroups: SDG improved (subgroup 1; N = 12 (55%)) and SDG worsened (subgroup 2; N = 10 (45%)). Group 1, compared to subgroup 2, required a lower insulin dose (Δbasal insulin dose = -8.0 vs. 6.3%; p <0.05) and had a lower frequency of hypoglycemia (27% vs. 64%, hypoglycemias/days evaluated; p <0.01). CONCLUSION: Our study suggests a relation between VD supplementation, improved glycemic variability, lower insulin needs and lower frequency of hypoglycemia in patients with T1DM.

Relationship between endothelial nitric oxide synthase (eNOS) and natural history of intracranial aneurysms: meta-analysis.

The aneurysmal subarachnoid hemorrhage is a major public health problem described as a sudden drastic event with no warning symptoms and high morbidity and mortality rates. The role of the endothelial isoform of nitric oxide synthase gene polymorphism in intracranial aneurysms (IAs) is still a matter of controversy with divergent findings among European, American, and Asian populations. Our study purposed to test the association between intracranial aneurysms formation and nitric oxide gene polymorphisms through a systematic review and meta-analysis. Systematic search on Medline, Lilacs, and EMBASE was performed. The primary search resulted in 139 papers, out of which 9 met our inclusion criteria after a full text analysis. The dominant T786C model found a significant association with IA (OR 1.22, 95 % CI 1.04-1.44, p = 0.01), so did studies of the recessive T786C model (OR 0.37, 95 % CI 0.30-0.45, p < 0.0001) but with opposite effect. Our findings support the presence of the T786C polymorphism as a predictor for the development of intracranial aneurysm in the cerebral vascular system. More studies are necessary in order to elucidate the pathways of the endothelial nitric oxide synthase (eNOS) in cerebrovascular diseases and in defining how different allelic combinations of the eNOS gene single-nucleotide polymorphism (SNP) could favor this pathological process.

Periodontitis and Alzheimer's Disease: A Possible Comorbidity between Oral Chronic Inflammatory Condition and Neuroinflammation.

Periodontitis is an oral chronic infection/inflammatory condition, identified as a source of mediators of inflammation into the blood circulation, which may contribute to exacerbate several diseases. There is increasing evidence that inflammation plays a key role in the pathophysiology of Alzheimer's disease (AD). Although inflammation is present in both diseases, the exact mechanisms and crosslinks between periodontitis and AD are poorly understood. Therefore, this article aims to review possible comorbidity between periodontitis and AD. Here, the authors discuss the inflammatory aspects of periodontitis, how this oral condition produces a systemic inflammation and, finally, the contribution of this systemic inflammation for worsening neuroinflammation in the progression of AD.

Albuminuria Reduction after High Dose of Vitamin D in Patients with Type 1 Diabetes Mellitus: A Pilot Study.

BACKGROUND: Some studies suggest an association between diabetic kidney disease (DKD) and vitamin D (VD), but there is no data about the effect of high dose of VD on DKD in type 1 diabetes mellitus (T1DM). Our pilot study aims to evaluate albuminuria reduction in patients with T1DM supplemented with high dose of VD. METHODS: 22 patients received doses of 4,000 and 10,000 IU/day of cholecalciferol for 12 weeks according to patient's previous VD levels. They were submitted to continuous glucose monitoring system, 24 hours ambulatory blood pressure monitoring and urine albumin-to-creatinine ratio before and after VD supplementation. RESULTS: There was a reduction of DKD prevalence at the end of the study (68 vs 32%; p = 0.05), with no changes on insulin doses, glycated hemoglobin, glycemic variability and blood pressure values. A correlation between percentage variation of VD levels (ΔVD) and albuminuria at the end of the study was presented (r = -0.5; p < 0.05). Among T1DM patients with DKD at the beginning of the study, 8/13 (62%) had their DKD stage improved, while the other five ones (38%) showed no changes (p < 0.05). CONCLUSION: Our pilot study suggests an association between VD high dose supplementation, lower prevalence and improvement in stages of DKD in T1DM.

Vitamin D on Early Stages of Diabetic Kidney Disease: A Cross-sectional Study in Patients with Type 1 Diabetes Mellitus.

CONTEXT: Genetic and environmental factors are involved in the pathogenesis of type 1 diabetes mellitus (T1DM), and vitamin D (VD) deficiency appears as a candidate to risk factor for developing diabetic kidney disease (DKD). OBJECTIVE: The purpose of study was to evaluate the existence of an association between low levels of VD and the presence and degree of DKD in T1DM. PATIENTS AND METHODS: We performed a cross-sectional study, between November 2014 and December 2015. Levels of 25(OH)D and albuminuria were analyzed in 37 patients with T1DM and normal glomerular filtration rate. Thirty-six subjects were evaluated as a control group. RESULTS: Patients with T1DM and hypovitaminosis D had higher levels of albuminuria compared to those with normal VD levels [albuminuria (log10) = 1.92 vs. 1.44; p < 0.05]. When we have separated the group of patients according to stage of DKD in patients with normo, micro, and macroalbuminuria, there are lower levels of 25(OH)D in the last when compared to the first two groups (26.7 ± 6.2, 24.8 ± 7.0, and 15.9 ± 7.6 ng/ml; p < 0.05, respectively). In T1DM group, we have found correlations between VD levels and both albuminuria and DKD stages (r = -0.5; p < 0.01 and r = -0.4; p < 0.05, respectively). A simple linear regression model, with albuminuria as the dependent variable and VD as an independent variable, showed r2 = 0.2 and p < 0.01. CONCLUSION: Our data suggest an association between reduced levels of VD and the presence and severity of DKD.

A fatal case of pulmonary infection by Mycobacterium colombiense in Para State, Amazon Region, Brazil.

Mycobacterium avium complex (MAC) is a heterogeneous group of species found in several environmental sources and that exhibit variable degrees of pathogenicity. Among the MAC members, Mycobacterium colombiense has been related to pulmonary disease and disseminated infection in HIV-infected patients in Colombia. Lymphadenopathy cases have also been reported. We have described a fatal case of M. colombiense pulmonary disease in a Brazilian patient without evidence of HIV infection or other known causes of immunosuppression.

Health-related quality of life in people with type 1 Diabetes Mellitus: data from the Brazilian Type 1 Diabetes Study Group.

BACKGROUND: Type 1 Diabetes Mellitus (Type 1 DM) affects the psychological and emotional well-being of patients and their families. This study aims to evaluate the health- related quality of life (HRQoL) of people with Type 1 DM in Brazil, a country of continental proportions, using the EuroQol questionnaires. METHODS: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group, by analyzing EuroQol scores from 3,005 participants with Type 1 DM, in 28 public clinics in Brazil. Data on demography, economical status, chronic complications, glycemic control and lipid profile were also collected. RESULTS: The assessment of HRQoL by the EuroQol showed that the average score assigned to general health in Brazil is markedly lower than those found in two other Type 1 DM population-based studies conducted in Europe (EQ-VAS from the Netherlands, the United Kingdom and Brazil were 80.8 ± 15.2, 75.1 ± 18.4 and 72.5 ± 22, respectively). Additionally, our data suggest that a better glycemic control could positively impact the HRQoL of people with Type 1 DM, implying that each 1 % reduction in glycated haemoglobin might lead to an increase of 1.5 points in general health status assessed by the EuroQol. CONCLUSIONS: This is a population-based study evaluating the HRQoL of people with Type 1 DM in Brazil. Our data indicate a worse quality of health of people with Type 1 DM in Brazil in comparison to Europe, and suggest that a better glycemic control could positively impact the HRQoL of these individuals. However, this study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of these people.

In Vitro Cytoprotective Effects and Antioxidant Capacity of Phenolic Compounds from the Leaves of Swietenia macrophylla.

Swietenia macrophylla (mahogany) is a highly valued timber species, whereas the leaves are considered to be waste product. A total of 27 phenolic compounds were identified in aqueous extracts from mahogany leaves by comparing retention times and mass spectra data with those of authentic standards using LC-ESI-MS/MS. Polyphenols play an important role in plants as defense mechanisms against pests and pathogens and have potent antioxidant properties. In terms of health applications, interest has increased considerably in naturally occurring antioxidant sources, since they can retard the progress of many important neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. The antioxidant capacities of two aqueous extracts, M1 (decoction) and M2 (infusion), were measured using TEAC and Folin-Ciocalteau methods. Additionally, M1 was used in order to investigate its potential cytoprotective effects on an in vitro model of neurodegeneration, by using primary cerebellar cultures exposed to methyl mercury (MeHg). Under experimental sub-chronic conditions (72 h), concomitant exposure of the same cultures to MeHg and M1 extract resulted in a statistically significant increase in cell viability in all three concentrations tested (10, 50 and 100 µg/mL), strongly suggesting that due to its high content of antioxidant compounds, the M1 extract provides significant cytoprotection against the MeHg-induced in vitro neurotoxicity.

Health-related quality of life in patients with type 1 diabetes mellitus in the different geographical regions of Brazil: data from the Brazilian Type 1 Diabetes Study Group.

BACKGROUND: In type 1 diabetes mellitus (T1DM) management, enhancing health-related quality of life (HRQoL) is as important as good metabolic control and prevention of secondary complications. This study aims to evaluate possible regional differences in HRQoL, demographic features and clinical characteristics of patients with T1DM in Brazil, a country of continental proportions, as well as investigate which variables could influence the HRQoL of these individuals and contribute to these regional disparities. METHODS: This was a retrospective, cross-sectional, multicenter study performed by the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG), by analyzing EuroQol scores from 3005 participants with T1DM, in 28 public clinics, among all geographical regions of Brazil. Data on demography, economic status, chronic complications, glycemic control and lipid profile were also collected. RESULTS: We have found that the North-Northeast region presents a higher index in the assessment of the overall health status (EQ-VAS) compared to the Southeast (74.6 ± 30 and 70.4 ± 19, respectively; p < 0.05). In addition, North-Northeast presented a lower frequency of self-reported anxiety-depression compared to all regions of the country (North-Northeast: 1.53 ± 0.6; Southeast: 1.65 ± 0.7; South: 1.72 ± 0.7; Midwest: 1.67 ± 0.7; p < 0.05). These findings could not be entirely explained by the HbA1c levels or the other variables examined. CONCLUSIONS: Our study points to the existence of additional factors not yet evaluated that could be determinant in the HRQoL of people with T1DM and contribute to these regional disparities.

Annonacin, a natural lipophilic mitochondrial complex I inhibitor, increases phosphorylation of tau in the brain of FTDP-17 transgenic mice.

Both genetic and environmental factors likely contribute to the neuropathology of tauopathies, but it remains unclear how specific genetic backgrounds affect the susceptibility towards environmental toxins. Mutations in the tau gene have been associated with familial tauopathies, while annonacin, a plant-derived mitochondrial inhibitor, has been implicated in an environmental form of tauopathy. We therefore determined whether there was a pathogenic synergy between annonacin exposure and the expression of the R406W-tau mutation in transgenic mice. We found that annonacin exposure caused an increase in the number of neurons with phosphorylated tau in the somatodendritic compartment in several brain areas in R406W(+/+) mice as opposed to mice that had only the endogenous mouse tau (R406W(-/-)). Western blot analysis demonstrated a concomitant increase in total tau protein without increase in tau mRNA, but reduced proteasomal proteolytic activity in R406W(+/+), but not R406W(-/-) mice, upon annonacin-treatment. Phosphorylated tau levels exceeded the increase in total tau protein, along with increased levels of different tau kinases, foremost a striking increase in the p25/p35 ratio, known to activate the tau kinase Cdk5. In summary, we observed a synergistic interaction between annonacin exposure and the presence of the R406W-tau mutation, which resulted in reduced degradation, increased phosphorylation and redistribution of neuronal tau.

Number and distribution of neurons in the retinal ganglion cell layer in relation to foraging behaviors of tyrant flycatchers.

The tyrant flycatchers represent a monophyletic radiation of predominantly insectivorous passerine birds that exhibit a plethora of stereotyped prey capture techniques. However, little is known about their retinal organization. Using retinal wholemounts, we estimated the total number and topography of neurons in the ganglion cell layer in the generalist yellow-bellied elaenia (Elaenia flavogaster) and the up-hover-gleaner mouse-colored tyrannulet (Phaeomyias murina) with the optical fractionator method. The mean estimated total number of neurons in the ganglion cell layer was 4,152,416 +/- 189,310 in E. flavogaster and 2,965,132 +/- 354,359 in P. murina. Topographic maps of isocounting lines revealed a similar distribution for both species: a central fovea and a temporal area surrounded by a poorly defined horizontal streak. In addition, both species had increased numbers of giant ganglion cells in the dorsotemporal retina forming an area giganto cellularis. In E. flavogaster, these giant ganglion cells were also distributed across the nasal and ventral retinal peripheries, which is in agreement with the generalist habits of this species. However, in P. murina these cells were rarely seen along the nasal and ventral peripheries, possibly reflecting a lesser need to perceive movement because this species captures stationary insects resting on foliage. Thus, we suggest that the retinas of the tyrant flycatchers in the present study show a general common pattern of neuron distribution in the ganglion cell layer irrespective of their foraging habits. We also suggest that the distribution of giant ganglion cells is indicative of the visual requirements of the species.