Memory support training and lifestyle modifications to promote healthy aging in persons at risk for Alzheimer's disease: a digital application supported intervention (Brain Boosters).

BACKGROUND: Evidence-based interventions to protect against cognitive decline among older adults at risk for Alzheimer's disease and related dementias (ADRD) are urgently needed. Rehabilitation approaches to support memory and behavioral/lifestyle interventions are recognized as promising strategies for preserving or improving cognitive health, although few previous interventions have combined both approaches. This paper describes the protocol of the Brain Boosters intervention, which synergistically combines training in compensatory and healthy lifestyle behaviors and supports implementation and tracking of new behaviors with a digital application. METHODS: The study utilizes a single-site, single-blinded, randomized controlled design to compare a structured lifestyle and compensatory aid intervention to an education-only self-guided intervention. We plan to enroll 225 community-dwelling adults (25% from underrepresented groups) aged 65 + who endorse subjective cognitive decline (SCD) and low baseline levels of healthy lifestyle behaviors. Both interventions will be administered in group format, consisting of 15 two-hour classes that occur weekly for ten weeks and taper to bi-monthly and monthly, for an intervention duration of 6 months. Participants in both interventions will receive education about a variety of memory support strategies and healthy lifestyle behaviors, focusing on physical and cognitive activity and stress management. The structured intervention will also receive support in adopting new behaviors and tracking set goals aided by the Electronic Memory and Management Aid (EMMA) digital application. Primary outcomes include global cognition (composite of memory, attention, and executive function tests) and everyday function (Everyday Cognition Questionnaire). Data will be collected at baseline and outcome visits, at approximately 6, 12, and 18 months. Qualitative interviews, self-report surveys (e.g., indicators of self-determination, health literacy) and EMMA data metrics will also be used to identify what components of the intervention are most effective and for whom they work. DISCUSSION: Successful project completion will provide valuable information about how individuals with SCD respond to a compensation and preventative lifestyle intervention assisted by a digital application, including an understanding of factors that may impact outcomes, treatment uptake, and adherence. The work will also inform development, scaling, and personalization of future interventions that can delay disability in individuals at risk for ADRD. TRIAL REGISTRATION: ClinicalTrials.gov. (NCT05027789, posted 8/30/2021).

Machine learning for predicting chronic diseases: a systematic review.

OBJECTIVES: We aimed to review the literature regarding the use of machine learning to predict chronic diseases. STUDY DESIGN: This was a systematic review. METHODS: The searches included five databases. We included studies that evaluated the prediction of chronic diseases using machine learning models and reported the area under the receiver operating characteristic curve values. The Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis scale was used to assess the quality of studies. RESULTS: In total, 42 studies were selected. The best reported area under the receiver operating characteristic curve value was 1, whereas the worst was 0.74. K-nearest neighbors, Naive Bayes, deep neural networks, and random forest were the machine learning models most frequently used for achieving the best performance. CONCLUSION: We found that machine learning can predict the occurrence of individual chronic diseases, progression, and their determinants and in many contexts. The findings are original and relevant to improve clinical decisions and the organization of health care facilities.

Effects of cryolipolysis with adiposity plates located with the Crioplace concept in women.

BACKGROUND: Cryolipolysis with plates is a method of applying cooling without a vacuum system, which can be used in regions with less chance of forming a "crease." OBJECTIVE: To investigate the effects of cryolipolysis using a plate-shaped applicator (Crioplac) in the treatment of fat. MATERIALS AND METHODS: This is an experimental study in which women aged 25 to 45 years with adiposity located in the abdomen participated. Two applications of 75 min were made, using 04 plates in the abdomen regions, with -4 degree C being programmed as a temperature parameter. Anthropometric and ultrasound assessments were performed, and a satisfaction questionnaire on the validated treatment was conducted. The reassessments were performed 30 and 60 days after the first intervention. RESULTS: A reduction in adiposity was observed in the measurements of perimetry, plicometry and abdominal ultrasound (p<0.05). It was found that about 62.5% of the volunteers reported an improvement in water retention, about 62.5% reported the presence of loose clothing, and 31.3% reported satisfaction with the results obtained. It was observed that 18.5% of the volunteers reported that the treatment was excellent. CONCLUSION: The Crioplace method proved to be effective in reducing adiposity, with a high clinical satisfaction with the reduction in body measurements.

Effects of Cryolipolysis with Plates in Localized Adiposity with the CrioPlace Concept.

BACKGROUND: Plate cryolipolysis is a method of applying cooling without a vacuum system, which can be used in regions with less possibility of skin suction or fibrosis. OBJECTIVE: To investigate the effects of cryolipolysis with the use of plate-shaped applicators (CrioPlaceTM) for localized fat treatment. METHODS: The sample consisted of men aged 20 to 45 years with complaints of localized adiposity in the abdominal region and flanks. Two plates were positioned in the flank and abdomen regions, respectively. They received two 60-min applications in the temperature of -2°C. The anthropometric, thermographic and ultrasound assessments were performed, and a satisfaction questionnaire was applied after treatment. The re-evaluations occurred 30 and 60 days after the first intervention. RESULT: A reduction in adiposity was observed in flank region plicometry (p<0.05) and abdominal and flank ultrasound (p < 0.05). About 66.7% of the volunteers reported less water retention, about 41.7% reported that their clothes were looser, and 100% reported overall satisfaction. Fifty percent rated the treatment as excellent and 58.3% felt improvement in overall aesthetics. CONCLUSION: The CrioPlaceTM method was effective in reducing localized adiposity, with clinical satisfaction of measurement reduction, both in plicometry and ultrasound analyses, with highlights to the flank region results.

Evolution of the genus Mimivirus based on translation protein homology and its implication in the tree of life.

The natural history of mimiviruses (i.e., viruses that are members of the Mimivirus genus) is a challenge for modern biology. A new domain of life to include these organisms has been proposed from analysis of gene conservation. We analyzed the evolutionary relationship of proteins involved in the translation system, and our data show that mimiviruses are a sister group of Eukarya. New data about the origins of Eukarya, in which Eukarya appears as a branch derived from the Archaea domain, were discussed, and we suggest that the mimiviruses emerged from the initial population that gave origin to Eukarya and that, in this way are not part of a new domain of life.

Effects of low-level laser therapy combined with toluidine blue on polysaccharides and biofilm of Streptococcus mutans.

The aim of this study was to evaluate the effect of a low-level laser therapy in combination with toluidine blue on polysaccharides and biofilm of Streptococcus mutans. S. mutans biofilms were formed on acrylic resin blocks. These biofilms were exposed eight times/day to 10 % sucrose, and two times/day, they were subjected to one of the following treatments: G1, 0.9 % NaCl as a negative control; G2, 0.12 % chlorhexidine digluconate (CHX) as a positive antibacterial control; and G3 and G4 antimicrobial photodynamic therapy (aPDT) combined with toluidine blue using dosages of 320 and 640 J/cm(2), respectively. The experiment was performed in triplicate. The biofilm formed on each block was collected for determination of the viable bacteria and concentration of insoluble extracellular polysaccharides (IEPS) and intracellular polysaccharides (IPS). CHX and aPDT treatments were able to inhibit bacterial growth in comparison with negative control (p < 0.05). The aPDT treatment reduced the number of viable bacteria formed in the S. mutans biofilm, in a dose-dependent manner (p < 0.05). The concentration of IEPS and IPS in the biofilms formed in presence of aPDT did not differ each other or in comparison to CHX (p > 0.05). The results suggest that low-level laser therapy presents effects on biofilm bacteria viability and in polysaccharides concentration.

Qualitative analysis of the vaginal microbiota of healthy cattle and cattle with genital-tract disease.

The microbial community of the reproductive appara-tus, when known, can provide information about the health of the host. Metagenomics has been used to characterize and obtain genetic infor-mation about microbial communities in various environments and can relate certain diseases with changes in this community composition. In this study, samples of vaginal surface mucosal secretions were col-lected from five healthy cows and five cows that showed symptoms of reproductive disorders. Following high-throughput sequencing of the isolated microbial DNA, data were processed using the Mothur soft-ware to remove low-quality sequences and chimeras, and released to the Ribosomal Database Project for classification of operational taxo-nomic units (OTUs). Local BLASTn was performed and results were loaded into the MEGAN program for viewing profiles and taxonomic microbial attributes. The control profile comprised a total of 15 taxa, with Bacteroides, Enterobacteriaceae, and Victivallis comprising the highest representation of OTUs; the reproductive disorder-positive profile comprised 68 taxa, with Bacteroides, Enterobacteriaceae, His-tophilus, Victivallis, Alistipes, and Coriobacteriaceae being the taxa with the most OTU representation. A change was observed in both the community composition as well as in the microbial attributes of the profiles, suggesting that a relationship might exist between the patho-gen and representative taxa, reflecting the production of metabolites to disease progression.

Phylogenetic analysis of substrate-binding subunits in an osmoprotectant system.

Substrate-binding subunits are important components of the solute importation system, known as the osmoprotectant system, which consists of a membrane protein belonging to the ABC superfamily. These molecules recognize specific substrates that have different physiological roles in prokaryotes, i.e., roles that contribute to the survival of these organisms in environments with high concentrations of salt. Using the MEGA software, this study performed a phylogenetic analysis of 431 nucleotide sequences of these subunits, orthologous to each other, collected from the http://www.genome.jp/kegg/ database. This analysis allowed phylogenetic trees to be generated, clearly demonstrating that there was horizontal transfer of some genes through sharing by different organisms. Furthermore, two probable ancestral sequences were generated that showed homology with permeases that transport choline, glycine betaine, and carnitine, which are trimethylamines currently present in various prokaryotes. Therefore, this system probably arose in prokaryotic organisms with the basic function of capturing nutrients, and by performing this basal function and being shared with other organisms, it was fixed in the genome. However, because of prokaryote habitat diversification, this system contributed decisively to the adaptation of these organisms to different environments, especially environments that had a high salt concentration, thus acting as an osmoprotection system, which is how they are currently categorized.

Isolation, molecular characteristics and disinfection of methicillin-resistant Staphylococcus aureus from ICU units in Brazil.

The aim of the present study was to isolate S. aureus strains resistant to antibiotics, characterize the genotype profiles of resistance staphylococci, and evaluate the efficacy of antiseptic agents and disinfectants used in two public hospitals of Vitoria da Conquista, Bahia, Brazil. Clinical samples were obtained from ICU environments and equipment surfaces in two public hospitals in Vitoria da Conquista. Broth cultures were plated onto mannitol salt agar, and antimicrobial susceptibility testing was performed by the broth microdilution method according to CLSI. MRSA strains were submitted to PCR for detecting the mecA gene. PCR products were purified and sequenced for SCCmec type identification. Moreover, the strains were tested for efficacy of different disinfectant solutions. S. aureus were isolated from 31 and 67 sites in each hospital, respectively. Among the isolates from hospital 1, 07 (22.6%) were resistant to oxacillin while 28 (41.8%) were resistant in hospital 2. Thirty-one were positive for the mecA gene. All isolates showed SCCmec type III genotype characteristics of the Brazilian epidemic clone. In disinfectant tests, sodium hypochlorite (0.5, 1.0 and 2.0%), 2% chlorhexidine gluconate, quaternary ammonium, peracetic acid and formaldehyde were effective against the isolates tested. The strains showed higher resistance to vinegar (4% acetic acid), alcohol and glutaraldehyde. The findings of this study should assist in reducing the occurrence of nosocomial infections and therefore the morbidity, mortality and socio-economic burden caused by prolonged hospitalization.

Intrasubject reproducibility of functional MR imaging activation in language tasks.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the reproducibility of functional MR imaging (fMRI) activation (volume and laterality) within both inferior frontal and temporoparietal regions of interest for both receptive and expressive language tasks. METHODS: Ten healthy volunteers participated in fMRI experiments for 6 language tasks: verb generation, confrontation naming, semantic decision making, visual sentence comprehension, auditory sentence comprehension, and story listening. Each subject was scanned during 2 separate sessions separated by a minimum of 4 weeks. Laterality of activation was defined by laterality indices (LIs), which were calculated by 2 methods: one method based on the measured volume of activation and the other method based on the F statistic of the activation. Reproducibility was calculated by using concurrence ratios for the volume of activation (R(overlap), R(volume)) and test-retest correlation for LIs. RESULTS: All tasks generated reproducible LIs within at least one of the regions of interest, but verb generation produced the highest test-retest correlations (r = 0.99) within both regions of interest. Verb generation was associated with the highest average concurrence ratios within the inferior frontal region of interest (R(overlap) = 45.2; R(volume) = 70.9). In general, the concurrence ratios were lower within the temporoparietal region of interest compared with the inferior frontal region of interest. LIs calculated with F statistics were more reproducible than the LIs calculated by activation volume. CONCLUSION: fMRI is able to provide reproducible LIs in both inferior frontal and temporoparietal regions for assessing hemispheric dominance in language processing. The volume of activation, especially within the temporoparietal regions, is less reproducible than the laterality of activation, so the former should be used with caution.

The hamster cheek pouch as a model of oral cancer for boron neutron capture therapy studies: selective delivery of boron by boronophenylalanine.

Herein we propose and validate the hamster cheek pouch model of oral cancer for boron neutron capture therapy (BNCT) studies. This model serves to explore new applications of the technique, study the biology and radiobiology of BNCT, and assess the uptake of boron compounds and response of tumor, precancerous tissue, and clinically relevant normal tissues. These issues are central to evaluating and improving the therapeutic gain of BNCT. The success of BNCT is dependent on the absolute amount of boron in the tumor, and the tumor:blood and tumor:normal tissue boron concentration ratios. Within this context, biodistribution studies are pivotal. Tumors were induced in the hamsters with a carcinogenesis protocol that uses dimethyl-1,2-benzanthracene and mimics spontaneous tumor development in human oral mucosa. The animals were then used for biodistribution and pharmacokinetic studies of boronophenylalanine (BPA). Blood, tumor, precancerous pouch tissue surrounding tumor, normal pouch tissue, tongue, skin, cheek mucosa, palate mucosa, liver, and spleen, were sampled at 0-12 h after administration of 300 mg BPA/kg. The data reveal selective uptake of BPA by tumor tissue and, to a lesser degree, by precancerous tissue. Mean tumor boron concentration was 36.9 +/- 17.5 ppm at 3.5 h and the mean boron ratios were 2.4:1 for tumor:normal pouch tissue and 3.2:1 for tumor:blood. Higher doses of BPA (600 and 1200 mg BPA/kg) increased tumor uptake. Potentially therapeutic absolute boron concentrations, and tumor:normal tissue and tumor:blood ratios can be achieved in the hamster oral cancer model using BPA as the delivery agent.

Methylene blue reverts multidrug resistance: sensitivity of multidrug resistant cells to this dye and its photodynamic action.

Photodynamic action has been advocated as an alternative treatment of tumors but the most common used dyes, hematoporphyrin derivatives, are substrate for P-glycoprotein. This study investigated the MDR-reverting properties of methylene blue (MB) and compared the sensitivity to its photodynamic action (PDA) in five cell lines that either express or do not express the MDR phenotype. MB was able to revert the MDR phenotype and there was no difference in sensitivity to MB-PDA between MDR and non-MDR cells, suggesting that MB has the advantage of being used simultaneously as a MDR reverser and a photodynamic agent.

Comparative analysis of two different subunits of antigen B from Echinococcus granulosus: gene sequences, expression in Escherichia coli and serological evaluation.

Two different Echinococcus granulosus antigen B subunits (AgB8/1 and AgB8/2) were characterized and the structure of the genes encoding these two proteins were compared. DNA sequences were expressed in Escherichia coli and the antigens' diagnostic value was then assessed. The genomic sequence of AgB8/1 has a 92 bp intron in the position corresponding to amino acid 16; the AgB8/2 genomic sequence presents a 68 bp intron in the position corresponding to amino acid 20. Both introns are located between the putative N-terminal hydrophobic sequence and the secreted peptide. A comparison between the AgB8/1 and AgB8/2 nucleotide sequences showed a 53.5% identity among exons and a 50% identity between introns. According to the molecular diversity analysis, the elapsed time since both genes shared a common ancestor would be around 4.2x10(7) years. When the native AgB and the two recombinant antigens (rAgB8/1 and rAgB8/2) were tested in an anti-IgG ELISA, the sensitivity of the native antigen B was 77.41% and its specificity was 81.9%, while rAgB8/1 showed 54.84% of sensitivity and 80.17% of specificity and rAg138/2 had an 83.87% sensitivity and a 98.28% specificity. Statistical analysis confirms that rAgB8/2 has a better performance than rAgB8/1 and native AgB in ELISA.

Selective uptake of p-borophenylalanine by undifferentiated thyroid carcinoma for boron neutron capture therapy.

Undifferentiated thyroid carcinoma (UTC) lacks an effective treatment. Boron neutron capture therapy (BNCT) is based on the selective uptake of 10B-boronated compounds by some tumors, followed by irradiation with an appropriate neutron beam. The radioactive boron originated (11B) decays releasing 7Li, gamma rays and alpha particles, and these latter will destroy the tumor. In order to explore the possibility of applying BNCT to UTC we have studied the biodistribution of BPA. In in vitro studies, the uptake of p-10borophenylalanine (BPA) by the UTC cell line ARO, primary cultures of normal bovine thyroid cells (BT), and human follicular adenoma (FA) thyroid was studied. No difference in BPA uptake was observed between proliferating and quiescent ARO cells. The uptake by quiescent ARO, BT, and FA showed that the ARO/BT and ARO/FA ratios were 4 and 5, respectively (p < 0.001). In in vivo studies, ARO cells were transplanted into the scapular region of NIH nude mice, and after 2 weeks BPA (350 or 600 mg/kg body weight) was injected intraperitoneally. The animals were sacrificed between 30 and 150 minutes after the injection. With 350 mg, tumor uptake was highest after 60 minutes and the tumor/normal thyroid and tumor/blood ratios were 3 and 5, respectively. When 600 mg/kg body weight BPA were administered, after 90 minutes the tumor/blood, tumor/normal thyroid, and tumor/distal skin ratios for 10B concentrations per gram of tissue were approximately 3, showing a selective uptake by the tumor. The present experimental results open the possibility of applying BNCT for the treatment of UTC.

Glucocorticoid hormone renders a rat glioma cell line sensitive to a G1 phase block by microtubule disrupting agents.

1. Hydrocortisone, a glucocorticoid hormone, renders C6 rat glioma cells (clone ST1) sensitive to a block by colchicine or nocodazole (microtubule disrupters) at the G1 phase of the cell cycle. Restimulation of DNA synthesis in hydrocortisone-treated glioma cells arrested at G0/G1 phase by serum step-down is inhibited (85%) by colchicine (0.4 microgram/ml) added during the first 6 h of restimulation by serum step-up. 2. Exponentially growing, hydrocortisone-treated glioma cell cultures when subjected to colchicine treatment accumulated mitoses for 16.5 h, resulting in two types of cell cycle blocked cells: mitotic (round, detached or poorly attached) and G1 phase cells (flat and well attached to the solid substrate). The latter reinitiated DNA synthesis 15 h after colchicine withdrawal. Plating efficiency assays showed that while the colchicine block was highly toxic for mitotic cells, the survival of G1 phase arrested cells was not affected. In conclusion, in these rat glioma cells, hydrocortisone reversibly makes G1 phase progress dependent on microtubule integrity. 3. Restimulation of DNA synthesis in "normal" 3T3 fibroblasts arrested at the G0/G1 phase by serum deprivation was not inhibited by colchicine when the drug was added at the time of serum step-up. However, 70% inhibition occurred when colchicine was added at 10 h of serum stimulation.

Cloning and characterization of Echinococcus granulosus (Cestode) EgactI and EgactII actin gene promoters and their functional analysis in the NIH3T3 mouse cell line.

We report here for the first time the structure and function of a promoter from a cestode. The ability of DNA fragments respectively encompassing the 935-bp and 524-bp regions upstream from the ATG codon from the EgactI and EgactII actin genes of Echinococcus granulosus to promote transcription was studied in the NIH3T3 mouse cell line. The results of transfection assays showed that both regions have strong promoter activity in these cells. The fragments were tested in both orientations and the 524-bp fragment of EgactII presented a bidirectional promoter activity. Deletion analysis of EgactI and EgactII promoters indicated the presence of regulatory regions containing putative silencer elements. These results indicate that both EgactI and EgactII promoters are functional and that the preliminary functional evaluation of E. granulosus and possibly of other cestode promoters can be performed in heterologous cell lines.

Expression of the VP3-VP1 sequence of foot-and-mouth disease virus in Escherichia coli.

1. cDNA recombinants containing the VP3 and VP1 sequences of foot-and-mouth disease virus were isolated and the VP3-VP1 sequence was reconstructed. 2. The reconstructed VP3-VP1 sequence was subcloned into expression vector pEX31b and a fusion protein of about 62,000 Da was expressed. 3. When injected into mice, the fusion protein was able to elicit the production of antibodies that recognized viral VP1 and VP3. 4. Antibodies present in sera from mice immunized with VP3-VP1 protein did not neutralize the foot-and-mouth disease virus in vitro.

[Biplane transesophageal echocardiography. Experience with 130 outpatients]. / Ecocardiografia transesofágica biplanar. Experiência em 130 pacientes ambulatoriais.

PURPOSE: To analyse the utility of transesophageal echocardiography (TEE) as a complementary technique to transthoracic echocardiographic (TTE) comparing results and additional informations. METHODS: One hundred and thirty consecutive outpatients (66 male) submitted to TEE, with age ranging from 12 to 84 years were studied. Patients were grouped according to the main indication: evaluation of prosthetic valves, 21 patients; cardiac source of emboli, 43; diseases of the aorta, 17; infective endocarditis, 14; congenital heart diseases, 14 and other abnormalities in 21 patients. RESULTS: TEE provided additional and important information in all groups. Perivalvular leakage was observed in 42.1% of patients with prosthetic valves. Vegetations were detected in 45.5% of the suspected cases of endocarditis (missed by TTE). Dissection of aorta was diagnosed in 35.2% of patients with suspected disease and atrial septal defect was successfully recognized in 80% of the cases. No complications were observed. CONCLUSION: TEE is a safe and usefull complementary non-invasive diagnostic tool in the assessment of structures such as left atrium, left atrial appendage, thoracic aorta, prosthetic valves and in the investigation of infective endocarditis.

[Alternative to bromocriptine (BEC) management in patients with prolactinoma and intolerance to oral BEC]. / Alternativa de manejo con bromocriptina (BEC) en pacientes con prolactinoma e intolerancia a BEC oral.

Currently, the treatment of choice in cases of prolactinoma, is oral administration of bromocriptine mesilate, (BEC*), which, in a majority of cases, obtains satisfactory results. However, there do exist patients who show a clear intolerance to the oral administration of the medication in spite of low doses and other strategies. This leaves trans-sphenoidal surgery as the sole alternative since access to other dopamine-agonists medications is usually limited and the injection preparation of BEC is still in the experimental stages. This study follows the case histories of eleven patients who showed a clear intolerance to the oral administration of BEC and who would not accept or were otherwise disqualified from having hypophyseal surgery. Instead, their cases were handled through another alternative, the vaginal administration of BEC. The patients involved had an average age of 32 ranging from 26 to 44 years of age. All showed an important reduction in prolactinemia levels after the seventh day of vaginal administration of BEC. From an initial average high of 121.3 +/- 21.2 ng/ml levels were reduced after one week to 21.2 +/- 4.7 ng/ml, after ten days to 14.7 and after one month to 15.7 ng/ml. Patients were kept under observation for a twelve month period, during which time a significant reduction was noted in six patients, four became pregnant and one, finally rejected vaginal treatment. In every case, the bothersome side effects of the medication, which led to use of the alternative method of administration, specially the gastro-intestinal problems, subsided. This may be an interesting alternative for those patients with prolactinoma and evident intolerance to oral BEC.

[Living with an ostomy: a preliminary study]. / Vivendo com um ostoma: um estudo preliminar.

This study reveals some aspects of ostomy patients life experience. The data were obtained by using the participant observation technique during the monthly meeting session of the Ostomy Patients Association from July 1989 to August 1991. The findings showed that the ostomized patients were concerned with: 1) the ostomy pouch (how to get it); 2) other persons opinion about ostomized patients; 3) their sexuality, and stoma care. The patients perceived themselves as physically disable and inferior persons. Some of them perceived themselves as having a normal life. Other patients also had to cope with the stigma of cancer.