Phenotyping Superagers Using Resting-State fMRI.

BACKGROUND AND PURPOSE: Superagers are defined as older adults with episodic memory performance similar or superior to that in middle-aged adults. This study aimed to investigate the key differences in discriminative networks and their main nodes between superagers and cognitively average elderly controls. In addition, we sought to explore differences in sensitivity in detecting these functional activities across the networks at 3T and 7T MR imaging fields. MATERIALS AND METHODS: Fifty-five subjects 80 years of age or older were screened using a detailed neuropsychological protocol, and 31 participants, comprising 14 superagers and 17 cognitively average elderly controls, were included for analysis. Participants underwent resting-state-fMRI at 3T and 7T MR imaging. A prediction classification algorithm using a penalized regression model on the measurements of the network was used to calculate the probabilities of a healthy older adult being a superager. Additionally, ORs quantified the influence of each node across preselected networks. RESULTS: The key networks that differentiated superagers and elderly controls were the default mode, salience, and language networks. The most discriminative nodes (ORs > 1) in superagers encompassed areas in the precuneus posterior cingulate cortex, prefrontal cortex, temporoparietal junction, temporal pole, extrastriate superior cortex, and insula. The prediction classification model for being a superager showed better performance using the 7T compared with 3T resting-state-fMRI data set. CONCLUSIONS: Our findings suggest that the functional connectivity in the default mode, salience, and language networks can provide potential imaging biomarkers for predicting superagers. The 7T field holds promise for the most appropriate study setting to accurately detect the functional connectivity patterns in superagers.

The Brain Metabolic Signature in Superagers Using In Vivo 1H-MRS: A Pilot Study.

BACKGROUND AND PURPOSE: Youthful memory performance in older adults may reflect an underlying resilience to the conventional pathways of aging. Subjects having this unusual characteristic have been recently termed "superagers." This study aimed to explore the significance of imaging biomarkers acquired by 1H-MRS to characterize superagers and to differentiate them from their normal-aging peers. MATERIALS AND METHODS: Fifty-five patients older than 80 years of age were screened using a detailed neuropsychological protocol, and 25 participants, comprising 12 superagers and 13 age-matched controls, were statistically analyzed. We used state-of-the-art 3T 1H-MR spectroscopy to quantify 18 neurochemicals in the posterior cingulate cortex of our subjects. All 1H-MR spectroscopy data were analyzed using LCModel. Results were further processed using 2 approaches to investigate the technique accuracy: 1) comparison of the average concentration of metabolites estimated with Cramer-Rao lower bounds <20%; and 2) calculation and comparison of the weighted means of metabolites' concentrations. RESULTS: The main finding observed was a higher total N-acetyl aspartate concentration in superagers than in age-matched controls using both approaches (P = .02 and P = .03 for the weighted means), reflecting a positive association of total N-acetyl aspartate with higher cognitive performance. CONCLUSIONS: 1H-MR spectroscopy emerges as a promising technique to unravel neurochemical mechanisms related to cognitive aging in vivo and providing a brain metabolic signature in superagers. This may contribute to monitoring future interventional therapies to avoid or postpone the pathologic processes of aging.

Differential responses of genes and enzymes associated with ROS protective responses in the sugarcane smut fungus.

The fungal pathogen Sporisorium scitamineum causes sugarcane smut disease. We have previously shown that resistant sugarcane plants induce ROS, coinciding with a delay in fungal colonization. Here, we investigated whether the fungus modifies the enzymatic antioxidant system in vitro and when colonizing sugarcane tissues in response to ROS. In vitro, the exposure to ROS did not affect cell integrity, and a combination of superoxide dismutases (SOD) and catalases (CAT) were active. In vitro, the fungus did not alter the expression of the transcriptional regulator Yap1 and the effector Pep1. The fungus activated distinct enzymes when colonizing plant tissues. Instead of CAT, S. scitamineum induced glutathione peroxidase (Gpx) expression only when colonizing smut-resistant plants. Yap1 had an earlier expression in both smut-susceptible and -resistant plants, with no apparent correlation with the expression of antioxidant genes sod, cat, gpx, or external redox imbalance. The expression of the effector pep1 was induced only in smut-resistant plants, potentially in response to ROS. These results collectively suggest that S. scitamineum copes with oxidative stress by inducing different mechanisms depending on the conditions (in vitro/in planta) and intensity of ROS. Moreover, the effector Pep1 is responsive to the stress imposed only by the sugarcane resistant genotype.

Acid diterpenes from Copaiba oleoresin (Copaifera langsdorffii): Chemical and plasma stability and intestinal permeability using Caco-2 cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Copaiba oleoresin has been used in folk medicine in the treatment of bronchitis, syphilis, skin diseases and ulcers due to its anti-inflammatory and antiseptic activities, but there is no information about major compounds oral absorption to support the traditional use. AIM OF STUDY: Considering the potential of copalic (CA) and kaurenoic acid (KA) - major biological activity (in vitro) diterpenes found in the oleoresin, this study aimed to evaluate the intestinal permeability of CA and KA using Caco-2 cells model as predictive test for oral drug absorption. MATERIALS AND METHODS: Chemical stability at pH 1.2 and 7.4 and plasma stability were evaluated to mimic physiological conditions of the gastrointestinal tract. The intestinal permeability of CA and KA was evaluated in Caco-2 cells in the presence and absence of the P-glycoprotein inhibitor verapamil. RESULTS: CA and KA were rapidly degraded at pH 1.2 (0.2 M Clark-Lubs buffer). At pH 7.4 (0.1 M phosphate buffer), CA was stable for up to 24 h and KA for up to 6 h. In human plasma, CA and KA can be considered stable for 24 h and 12 h at 37 °C, respectively. Caco-2 cells were considered viable when incubated with CA or KA in the range of 3.9-250 µM for 24 h. CA and KA exhibited moderate apparent permeability (Papp) of 4.67 (±0.08) × 10-6 cm/s and 4.66 (±0.04) × 10-6 cm/s, respectively. Simultaneous incubation with verapamil showed that P-glycoprotein does not play a relevant role on CA and KA oral absorption, with Papp of 4.48 (±0.26) × 10-6 cm/s and 5.37 (±0.72) × 10-6 cm/s observed for CA and KA, respectively. CONCLUSION: The oral absorption of both CA and KA is driven by mainly passive permeability, is not limited by p-glycoprotein, but enteric-coated dosage forms should be used to avoid chemical instability in the gastric pH.

The SLCO1A2 -189_-188InsA polymorphism reduces clearance of rocuronium in patients submitted to elective surgeries.

PURPOSE: Rocuronium (ROC) is a neuromuscular blocker mainly eliminated by biliary excretion dependent on organic anion transporting polypeptide 1A2 (OATP1A2) hepatocellular uptake. However, the influence of SLCO1A2 (gene encoding OATP1A2) genetic polymorphism on ROC pharmacokinetics was never described before. The objective of this work was to evaluate the influence of genetic polymorphisms of SLCO1A2 on the pharmacokinetics of rocuronium (ROC). METHODS: Patients undergoing elective surgeries under general anesthesia using rocuronium as a neuromuscular blocker were genotyped for SLCO1A2 polymorphisms in the coding region (41A>G, 382A>T, 404A>T, 502C>T, 516A>C, 559G>A, 830C>A, and 833delA) and in the promoter region (-1105G>A, -1032G>A, -715T>C, -361G>A, and -189_-188insA). Rocuronium pharmacokinetic parameters were estimated by non-compartmental analysis. RESULTS: None of the patients had heterozygous or homozygous variant of 404A>T, 382A>T, 502C>T, 833delA, 830C>A, 41A>G, and -715T>C. A linkage disequilibrium was found between -1105G>A and -1032G>A genotypes. Patients genotyped as -A or AA (n = 17) for SLCO1A2 -189_-188InsA showed reduced total clearance of ROC compared to patients genotyped as -/- (n = 13) (151.6 vs 207.1 mL/min, p ≤ 0.05). The pharmacokinetics parameters of ROC were not significantly different between other SLCO1A2 genotypes. CONCLUSION: SLCO1A2 -189_-188InsA polymorphism is related to the reduced clearance of rocuronium in patients submitted to elective surgeries under general anesthesia. TRIAL REGISTRATION: NCT 02399397 ( ClinicalTrials.gov ).

Reliability analysis of visual examinations carried out by school-teachers and a dental assistant in the detection of dental caries.

AIM: This study aims to investigate the reliability of examinations performed by teachers and by a dental assistant in detection of cavitated surfaces. METHODS: A sample of 168 students, aged 5-14 years, attending a public school in Duque de Caxias, Rio de Janeiro, was examined by persons with three different training backgrounds: a dentist, a dental assistant, and schoolteachers. Examinations were performed in the school with the aid of a tongue blade under natural light. Kappa statistics were estimated to assess agreement between the observers. Sensitivity, specificity, and positive and negative predictive value tests helped validate observations performed by the group of laypersons. RESULTS: The findings suggest satisfactory agreement with the dentist, with kappa values of 0.730 and 0.781 for the teachers and the dental assistant, respectively. The absence of cavities was easily detected (specificity = 96%). More caution is required in positive results indicated by the teachers or the dental assistant because these were not always confirmed subsequently (sensitivity = 76%) by the dentist. CONCLUSION: The aid of untrained personnel in dental epidemiology was shown to be a valid alternative for a signposting role.

Evolución de 1 año de un paciente rehabilitado con implantes oseointegrados de carga inmediata después de la resección quirúrgica de un cementoblastoma: reporte clínico / Clinical Report: patient’s progress one year after being treated with immediate loading bone integrated implants after removal of cementoblastomas

Se presenta un caso clínico correspondiente a un paciente con diágnostico de dos cementoblastomas, en el cual, posterior a la resección quirúrgica de ambos tumores, se rehabilitó con una prótesis sobre implantes de carga inmediata. Para esto instalaron 4 implantes, utilizando el sistema de Carga Inmediata Speed Máster (Conexão Sistema de Prótesis- São Paulo- Brazil) con la instalación de la prótesis 48 horas después de la cirugía. La evolución clínica y radiográfica fue seguida por 14 meses, comprobando que los implantes mantenían una condición adecuada(AU)

The authors present a clinical case of a patient with two cementoblastomas who was treated with four implants installed using Speed Master System. The prosthesis was seated 48 hours after surgery. The clinical and radiographic follow-up was performed 14 months later and it was determined that the implants were in satisfactory conditions(AU)

Toothache referred from auriculotemporal neuralgia: case report.

AIM: To present a 52-year-old male patient who complained of intense pain of short duration in the region of the left external ear and in the ipsilateral maxillary second molar that was relieved by blockade of the auriculotemporal nerve in the infratemporal fossa. SUMMARY: Extra- and intraoral physical examination revealed a trigger point that reproduced the symptoms upon finger pressure in the ipsilateral auriculotemporal nerve and in the outer auricular pavilion. The patient's medical history was unremarkable. The maxillary left second molar tooth was not responsive to pulp sensitivity testing and there was no pain upon percussion or palpation of the buccal sulcus. Periapical radiographs revealed a satisfactory root filling in the maxillary left second molar. On the basis of the clinical signs and symptoms, the auriculotemporal was blocked with 0.5 mL 2% lidocaine and 0.5 mL of a suspension containing dexamethasone acetate (8 mg mL(-1)) and dexamethasone disodium sulfate (2 mg mL(-1)), with full remission of pain 6 months later. The diagnosis was auriculotemporal neuralgia. KEY LEARNING POINT: Auriculotemporal neuralgia should be considered as a possible cause of nonodontogenic toothache and thus included in the differential diagnoses. The blockade of the auriculotemporal nerve in the infratemporal fossa is diagnostic and therapeutic. It can be achieved with a solution of lidocaine and dexamethasone.

Inspiratory muscular activation during threshold therapy in elderly healthy and patients with COPD.

UNLABELLED: Inspiratory muscles training in COPD is controversial not only in relation to the load level required to produce muscular conditioning effects but also in relation to the group of patients benefiting from the training. Consequently, inspiratory muscular response assessment during Threshold therapy may help optimizing training strategy. The objective of this study was to evaluate the participation of the diaphragm and the sternocleidomastoid (SMM) muscle to overcome with a 30% Threshold load using surface electromyography (sEMG) and to analyze the correlation between SMM activation, maximum strength level of inspiratory muscles (MIP) and obstruction degree in COPD patients (FEV1). We studied seven healthy elderly subjects, mean age of 68+/-4 years and seven COPD patients, FEV1 45+/-17% of the predicted value, with mean age 66+/-8 years. sEMG analysis of SMM muscles and diaphragm were obtained through RMS (root-mean-square) during three stages: pre-loading, loading and post-loading. RESULTS: In the COPD group, the RMS of the SMM increased 28% during load (p<0.05) while the RMS of the diaphragm remained constant. In the elderly there was a trend of a 11% increase in diaphragm activity and of 7% in SMM activity but, without reaching significance levels. SMM activity demonstrated good correlation with the obstruction level (r=-0.537). CONCLUSION: To overcome the load required by Threshold therapy, COPD patients demonstrated an increase of accessory muscles activity, represented by SMM. For the same relative load this increase seems to be proportional to the degree of pulmonary obstruction.

Genetic diversity in different populations of sloths assessed by DNA fingerprinting

In this study we analyzed a population of Bradypus torquatus with individuals originally distributed in different localities of Bahia, and two populations of B. variegatus with individuals from Bahia and Sõo Paulo States. Using the DNA fingerprinting method, we assessed the genetic variability within and between populations. Analysis of the DNA profiles revealed genetic similarity indices ranging from 0.34 ± 0.07 to 0.87 ± 0.04. Similar low levels of genetic variability were found only in isolated mammalian populations or among related individuals. This study presents the first analyses of genetic diversity in sloth populations

Genetic diversity in different populations of sloths assessed by DNA fingerprinting

In this study we analyzed a population of Bradypus torquatus with individuals originally distributed in different localities of Bahia, and two populations of B. variegatus with individuals from Bahia and São Paulo States. Using the DNA fingerprinting method, we assessed the genetic variability within and between populations. Analysis of the DNA profiles revealed genetic similarity indices ranging from 0.34 ± 0.07 to 0.87 ± 0.04. Similar low levels of genetic variability were found only in isolated mammalian populations or among related individuals. This study presents the first analyses of genetic diversity in sloth populations.

Neste estudo foram analisadas uma população de Bradypus torquatus composta por indivíduos provenientes de diferentes localidades do Estado da Bahia e duas populações de B. variegatus, uma na Bahia e outra em São Paulo. A estimativa da variabilidade genética dentro e entre as populações foi feita utilizando-se a técnica de DNA fingerprinting. A partir da análise dos padrões de bandas de DNA, foram calculados índices de similaridade genética que variaram de 0,34 ± 0,07 a 0,87 ± 0,04. Valores semelhantes, que indicam baixa variabilidade genética nas populações de preguiças analisadas, foram encontrados somente em populações de mamíferos isolados ou grupos de indivíduos aparentados. Este trabalho apresenta os primeiros resultados no estudo da diversidade genética em populações de preguiças.

Genetic diversity in different populations of sloths assessed by DNA fingerprinting.

In this study we analyzed a population of Bradypus torquatus with individuals originally distributed in different localities of Bahia, and two populations of B. variegatus with individuals from Bahia and São Paulo States. Using the DNA fingerprinting method, we assessed the genetic variability within and between populations. Analysis of the DNA profiles revealed genetic similarity indices ranging from 0.34 +/- 0.07 to 0.87 +/- 0.04. Similar low levels of genetic variability were found only in isolated mammalian populations or among related individuals. This study presents the first analyses of genetic diversity in sloth populations.

NADPH-diaphorase activity and nitric oxide synthase isoforms in the trophoblast of Calomys callosus.

The pattern of expression of a variety of placental nitric oxide synthase isoforms has contributed to elucidating the regulatory mechanisms of nitric oxide (NO) synthesis during gestation. The maintenance of vascular tone, attenuation of vasoconstriction, prevention of platelet and leukocyte adhesion to the trophoblast surface, and possible participation in uterine blood flow seem to be the main functions of NO generated at the fetal-maternal interface in humans and mice. Extending this knowledge to other rodent species commonly used as laboratory animals, in this study we focus on NADPH-diaphorase activity and the distribution of nitric oxide synthase isoforms (NOS) in the trophoblast cells of Calomys callosus during different phases of pregnancy. NADPH-diaphorase activity was evaluated cytochemically and the presence of NOS isoforms detected by immunohistochemistry. These techniques were performed on pre- and postimplantation embryos in situ and in vitro, as well as in placentae on d 14 and 18 of pregnancy. Neither NADPH-diaphorase activity nor inducible or endothelial NOS isoforms were found in pre-implanting embryos except after culturing for at least 48 h, when some of the embryonic cells were positive for the diaphorase reaction. On d 6.5 of pregnancy, trophoblast cells showed intense diaphorase activity both in situ and under in vitro conditions. A positive reaction was also found in the different placental trophoblast cells on d 14 and 18 of pregnancy. The inducible NOS (iNOS) isoform, but not the endothelial isoform, was immunodetected in trophoblast cells from the placenta and from postimplantation embryos in situ and under in vitro conditions. These results strongly suggest the production of NO by the iNOS isoform in the trophoblast of Calomys callosus after embryo implantation. The data also emphasise a possible role for the trophoblast in producing and releasing cytotoxic molecules at the fetal-maternal interface.

A giant phosphoprotein localized at the spongiome region of Crithidia luciliae thermophila.

A giant protein with an apparent molecular mass of 2,300-kDa was identified in the Triton X-100 soluble fraction of Crithidia luciliae thermophila. Polyclonal antibody raised against this protein reacted by immunoblot analysis with proteins of similar molecular mass in Crithidia fasciculata and Crithidia oncopelti. In addition, the antibody immunoprecipitates the protein either after in vivo phosphorylation with [32P]orthophosphoric acid or after metabolically labeling with [35S]methionine. Indirect immunofluorescence microscopy analysis performed either with fixed or with live parasites showed a single fluorescent spot at the level of the flagellar pocket region. Immunogold electron microscopy of thin sections of the parasite revealed that the antigen is localized at a restricted area of the spongiome, between the contractile vacuole and the flagellar pocket. Furthermore, Triton X-114 phase separation of whole cell membrane proteins, metabolically labeled with [35S]methionine, demonstrated that the giant protein remains in the aqueous phase. These results indicate that this phosphoprotein behaves as a peripheral membrane protein localized at the spongiome region, suggesting that it might be involved in the osmoregulatory process.

Microangiopathic complications in type 1 diabetes mellitus: differences in severity when isolated or associated with autoimmune polyendocrinopathies.

CONTEXT: The development and evolution of different chronic diabetic complications may present variations among the different types and conditions of this disease. OBJECTIVE: To evaluate the degree of microangiopathy in Type 1 diabetes mellitus (DM1) associated with autoimmune polyendocrinopathies (OSAD) or isolated DM1 (iDM1). PATIENTS: OSAD (n = 17) and iDM1 (n = 13) were over 15 years old at diagnosis of DM and were matched for diabetes duration (13.9 +/- 8.2 and 13.2 +/- 5.9 years respectively) and metabolic control (HbA1c: 6.4 +/- 1.9 and 6.8 +/- 1.4%). MAIN OUTCOME MEASURES: Urinary albumin excretion (UAE; ELISA), the inversion of serum creatinine (1/C) level and indirect ophthalmoscopy. RESULTS: Although the prevalence of hypertension was similar in both groups, the OSAD had inferior levels of UAE (7.4 +/- 2.5 vs. 17.3 +/- 9.2 micrograms/min; p < 0.05). Nephropathy was detected in 12% of the OSAD (none of them macroproteinuric) and in 39% of the iDM1. The UAE in the iDM1 correlated negatively with 1/C values (r = -0.7, p < 0.005), but the same did not occur in the OSAD (r = 0.2, ns). Among patients with retinopathy, the severe form was found in 29% of the OSAD and in 46% of the iDM1. CONCLUSIONS: OSAD was associated with a lower degree of microangiopathy, in spite of age at diagnosis, duration of diabetes and the metabolic control. In contrast with the iDM1, the increase in UAE of OSAD was not associated with reductions in GFR.

Compliance with supportive periodontal therapy.

Analysis of 1,280 private patient records from a periodontal clinic showed poor compliance with supportive periodontal therapy (SPT). Data were analyzed according to sex, age, and type of treatment (with or without periodontal surgery). Analysis showed that 25.2% of the patients never returned and among those who report for SPT, only 40.1% did so regularly; the percent of surgical cases was greater (70.7%) and those patients had better compliance (77.6%); compliance of women was greater (76.5%); abandonment of supportive periodontal treatment was high (66.7%), and compliance increased with age. Several suggestions concerning clinical procedures are offered with the objective of motivating patients to give the necessary importance to supportive periodontal therapy.