A novel lysosome-to-mitochondria signaling pathway disrupted by amyloid-ß oligomers.

The mechanisms of mitochondrial dysfunction in Alzheimer's disease are incompletely understood. Using two-photon fluorescence lifetime microscopy of the coenzymes, NADH and NADPH, and tracking brain oxygen metabolism with multi-parametric photoacoustic microscopy, we show that activation of lysosomal mechanistic target of rapamycin complex 1 (mTORC1) by insulin or amino acids stimulates mitochondrial activity and regulates mitochondrial DNA synthesis in neurons. Amyloid-ß oligomers, which are precursors of amyloid plaques in Alzheimer's disease brain and stimulate mTORC1 protein kinase activity at the plasma membrane but not at lysosomes, block this Nutrient-induced Mitochondrial Activity (NiMA) by a mechanism dependent on tau, which forms neurofibrillary tangles in Alzheimer's disease brain. NiMA was also disrupted in fibroblasts derived from two patients with tuberous sclerosis complex, a genetic disorder that causes dysregulation of lysosomal mTORC1. Thus, lysosomal mTORC1 couples nutrient availability to mitochondrial activity and links mitochondrial dysfunction to Alzheimer's disease by a mechanism dependent on the soluble building blocks of the poorly soluble plaques and tangles.

Malacofauna of lotic environments in the Northeast and Brazilian semiarid region: current knowledge and new records.

Despite the great diversity, economic and environmental importance of limnic mollusks, the group is still little investigated in the Brazilian semiarid region, especially in the state of Piauí. Thus, this work aims to gather information on the diversity of limnic mollusks in the Brazilian Northeast and the semiarid region, including new records for the state of Piauí, northeastern Brazil. For this, collections in the urban perimeter of the Itaim and Guaribas Rivers, municipalities of Itainópolis, and Picos, respectively, between October 2017 and September 2019. Besides, a literature review was conducted on studies of malacofauna in the Northeast and the Brazilian semiarid region. A total of 11 species from the classes Gastropoda and Bivalvia were collected on the rivers of Piauí, being the first record of Uncancylus concentricus for the Northeast region. For lotic environments in the state of Piauí, Drepanotrema schubarti, Pomacea canaliculata, Pisidium dorbignyi and Stenophysa marmorata were registered for the first time. Then, it was possible to verify that the Northeast of Brazil has 71 species registered, of which 34 occur in the semiarid. The diversity of species surveyed and the first record of the occurrence of several of them for the semiarid region demonstrate the importance of expanding studies involving this group to other areas. The present study is the first to gather and increase the information available on the fauna of limnic mollusks for the Northeast and Brazilian semiarid regions. The information gathered here may contribute to future research and to the species conservation and the environments they occupy, especially considering the presence of non- native and vector species.

Bioethical analysis to the therapeutic use of Cannabis: Integrative review.

INTRODUCTION:: Despite being considered as a contravention under some countries' legislation, the therapeutic use of Cannabis sativa has been growing in Brazil, due to the promising results observed in many pathologies. Such a scenario has fostered the need to deepen discussions on the subject and possibly revise legislation governing the substance use and access. OBJECTIVES:: Identify the types of stigma related to the therapeutic use of Cannabis and describe the strategies people use to overcome stigma. METHODS:: This integrative review was carried out in the databases PubMed, Scopus, CINAHL, MEDLINE, PsycINFO, Web of Science, and Cochrane Library, with 565 articles being retrieved. Triads' cross-check were done, first maintaining the "cannabis" and "therapeutic use" pair, added by "stigma," "bioethics," "ethics," "social consequences," and "legal consequences." The final selection resulted in six articles. ETHICAL CONSIDERATION:: However, the ethical issues that pervade and regulate decisions on this subject must be considered. RESULTS:: Different dimensions and types of stigma related to the therapeutic use of Cannabis have been identified. The bioethical principle of autonomy was an expression of citizenship and human rights, mitigating internal conflicts related to self-stigma and the effects of external stigma on the person's life. CONCLUSION:: It was possible to identify the types of stigma related to the therapeutic use of Cannabis is an internal dimension represented (self-stigma) and an external dimension, represented (social and structural stigmas) and to identify strategies adopted to face this stigma: skills training group for users, elaboration of laws and specific programs to clarify the therapeutic use of Cannabis with a greater social scope, and support for family members. Thus, contributing to the building of people's autonomy in a broader context of decision-making autonomy and executive autonomy will provide the development of people's capacity to perform complex tasks of self-management and, consequently, to continue promoting and preserving their decision-making process and their capacity to plan and perform tasks associated with managing their lives and their treatments.

Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-ß.

Extracellular plaques of amyloid-ß and intraneuronal neurofibrillary tangles made from tau are the histopathological signatures of Alzheimer's disease. Plaques comprise amyloid-ß fibrils that assemble from monomeric and oligomeric intermediates, and are prognostic indicators of Alzheimer's disease. Despite the importance of plaques to Alzheimer's disease, oligomers are considered to be the principal toxic forms of amyloid-ß. Interestingly, many adverse responses to amyloid-ß, such as cytotoxicity, microtubule loss, impaired memory and learning, and neuritic degeneration, are greatly amplified by tau expression. Amino-terminally truncated, pyroglutamylated (pE) forms of amyloid-ß are strongly associated with Alzheimer's disease, are more toxic than amyloid-ß, residues 1-42 (Aß(1-42)) and Aß(1-40), and have been proposed as initiators of Alzheimer's disease pathogenesis. Here we report a mechanism by which pE-Aß may trigger Alzheimer's disease. Aß(3(pE)-42) co-oligomerizes with excess Aß(1-42) to form metastable low-n oligomers (LNOs) that are structurally distinct and far more cytotoxic to cultured neurons than comparable LNOs made from Aß(1-42) alone. Tau is required for cytotoxicity, and LNOs comprising 5% Aß(3(pE)-42) plus 95% Aß(1-42) (5% pE-Aß) seed new cytotoxic LNOs through multiple serial dilutions into Aß(1-42) monomers in the absence of additional Aß(3(pE)-42). LNOs isolated from human Alzheimer's disease brain contained Aß(3(pE)-42), and enhanced Aß(3(pE)-42) formation in mice triggered neuron loss and gliosis at 3 months, but not in a tau-null background. We conclude that Aß(3(pE)-42) confers tau-dependent neuronal death and causes template-induced misfolding of Aß(1-42) into structurally distinct LNOs that propagate by a prion-like mechanism. Our results raise the possibility that Aß(3(pE)-42) acts similarly at a primary step in Alzheimer's disease pathogenesis.

Assistive technology and active aging according to professionals working in community groups. / Tecnologia assistiva e envelhecimento ativo segundo profissionais atuantes em grupos de convivência.

OBJECTIVE: To identify the knowledge of professionals about assistive technology and its importance in the elderly's life. METHOD: Exploratory descriptive qualitative study performed with professionals working in three community groups in the city of Cajazeiras (state of Paraíba/PB). Data were collected through an interview with semi-structured script and analyzed according to the Content Analysis Technique. RESULTS: Participation of 45 professionals. Four categories were identified, namely: Knowledge about assistive technology; Professionals' lack of knowledge about available assistive technologies for implementation in work with the elderly; Use of assistive technology by the elderly; Impact on professional practices after implementation of assistive technology. CONCLUSION: Some of professionals have knowledge about assistive technology and others make a wrong interpretation by confusing it with working instruments. In spite of the positive impact of assistive technology on certain professionals' practice, there is need for training in order to provide a better use of assistive technologies by the elderly.

mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease.

A major obstacle to presymptomatic diagnosis and disease-modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid-ß oligomers (AßOs) and tau, the precursors of plaques and tangles. We now report that CCR results from AßO-induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1-dependent tau phosphorylation, and that CCR can be prevented by insulin-stimulated activation of lysosomal mTORC1. AßOs were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by AßOs unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death.

Social representations of integrative community therapy by the elderly. / Representações sociais sobre terapia comunitária integrativa construídas por idosos.

OBJECTIVE: To elicit the social representations of the elderly regarding integrative community therapy (ICT). METHOD: This is an exploratory study conducted with 273 elderly people in a municipality of northeastern Brazil, in 2014. It is based on the theory of social representations and the free-association test for the inductor term "integrative community therapy". The data were processed using EVOC software and examined with the structural approach of social representations, followed by a similarity analysis and confrontation with literature. RESULTS: The organisation and meaning of the representations of ICT chiefly occurred through the core element: Group. CONCLUSION: The analysis revealed that the ICT is a support network for the elderly, where they feel they belong to a group and feel empowered through participation in the sessions.

Nursing Staff Members Mental's Health and Factors Associated with the Work Process: An Integrative Review.

BACKGROUND: The mental health of nursing staff members influences the work process outcomes. OBJECTIVE: Identify the work related factors that harms the nursing team's mental health. METHODS: Databases PubMed, Scopus, CINAHL and MEDLINE, by mating between the indexed descriptors in MeSH terms "mental health" and "occupational health nursing". 783 articles were rescued to give a final sample of 18 articles. Integrative review in order to identify factors associated with the work process of the nursing staff that negatively affects mental health. RESULTS: The main associated factors were work demands, psychological demands, violence, aggression, poor relationships with administrators, accidents involving the risk of exposure to HIV, stress and errors in the execution of labor activities. The main findings regarding the nursing staff's mental health were post-traumatic stress disorder, depression, stress, major depressive episode and generalized anxiety disorder. CONCLUSION: Occupational nurses need to understand the complexities of mental health problems and substance use among nursing staff members to recognize, identify and care for workers at risk and offer adequate mental health care. Although the researches interests in this theme have increased, proving that all these factors contribute to the risk to mental health of nursing professionals, the protective measures and care are being neglected by managers in both private and public network . The health of nursing workers in question here is one more challenge for a profession that takes care of others in need, therefore, requires some caring with their own health.

[Term base for nursing practices with elderly women with HIV/AIDS]. / Banco de termos para a prática de enfermagem com mulheres idosas com HIV/aids.

The aim of this study was to create a term base for nursing practices with elderly women with HIV/AIDS. This documental descriptive research was conducted at the Universidade Federal de Paraíba, from August 2012 to July 2013, based on a list of terms from the Integrated Plan to Combat the Feminization of AIDS and other STDs. These terms were cross-mapped with those of the International Classification for Nursing Practices 2011 (CIPEr 2011) and use of these terms in nursing practices was confirmed with the help of 15 participants. The base comprised 106 constant terms and 69 non-constant terms in the CIPEr 2011. Results revealed the need to reconsider nursing care for elderly women with HIV/AIDS in light of epidemiological changes in relation to aging and feminization of the disease. The term base will support the construction of more appropriate wording for nursing diagnoses, results and interventions for elderly women with HIV/AIDS.

Influence of Anaerobic Exercise in Type 1 Diabetes Mellitus Biomarkers: ASystematic Review.

AIM: Physical exercise is part of the type 1 diabetes mellitus (T1DM) treatment. However, this practice is still neglected due to the wide variety of glycemic responses under the influence of anaerobic exercise. Therefore, this study aimed to investigate the influence of anaerobic exercise on biomarkers of T1DM. METHODS: The systematic review was conducted on PubMed, Lilacs, and Embase, according to PRISMA. For this purpose, three groups of descriptors were used: Adults with T1DM, anaerobic physical exercise, and glycemic control. The search filter was set to human beings older than 18 years of age, longitudinal and cross-sectional studies, with studies published from 2000 to 2023 in English, Spanish, or Portuguese. Titles and abstracts were read independently by two reviewers, and then the articles were selected for this review. The Kappa coefficient was measured to evaluate the selection. RESULTS: A total of 738 articles were identified, and five were selected to be part of the review after applying the steps of the procedure. Some benefits were observed in fatigue reduction, absence of diabetic ketoacidosis requiring hospitalization, and enhancement of glucose monitoring during exercise. In the anaerobic workouts of the groups with T1DM, glycemic mean values ranged from 124.5-185.0 mg/dl, and glycated hemoglobin records ranged from 6.7-8.1%. CONCLUSION: Anaerobic exercise improved the biomarkers of T1DM, especially glycemic control, and the reduction of symptomatic hypoglycemic episodes. Anaerobic exercise can be performed by individuals with T1DM, suggesting an individualized training prescription and encouraging its practice associated with aerobic exercise.

Phlebotomine sand fly (Diptera: Psychodidae) fauna, blood meal source, and detection of Leishmania (Kinetoplastida: Trypanosomatidae) DNA in the Gurupi Biological Reserve, Eastern Amazon, Brazil.

This study was conducted in the Gurupi Biological Reserve (REBIO-Gurupi), the largest area of Amazon rainforest in Maranhão State, Brazil. The objectives were to survey the sand fly (Diptera: Psychodidae) fauna of REBIO-Gurupi, identify blood meal sources, and investigate the presence of Leishmania (Ross, 1903) (Kinetoplastida: Trypanosomatidae) DNA. Individuals were collected using Centers for Disease Control (CDC) light traps and black and white Shannon traps in May and Jun 2022 and Jan 2023. DNA was extracted from female sand flies and subjected to amplification and sequencing of cytochrome b molecular marker (CYTB) for identification of blood meal sources and the first internal transcribed spacer (ITS-1) of ribosomal DNA for Leishmania detection. A total of 514 sand flies individuals were sampled, of which 93 were identified at the genus or series level (9 taxa) and 421 were identified at the species level (24 taxa). Psychodopygus davisi (Root, 1934) (41.1%), Nyssomyia antunesi (Coutinho, 1939) (10.3%), and Psychodopygus (Mangabeira, 1941) Chagasi Series Barretto, 1962 (9.7%) were the most frequently collected. Human (Homo sapiens, Primates, Hominidae) and tapir (Tapirus terrestris, Perissodactyla, Tapiridae) DNA was detected in 10 female sand flies. Leishmania (Leishmania) infantum Cunha and Chagas, 1937 DNA was detected in 2 specimens of Ps. davisi. Given the presence of vectors of Leishmania in REBIO-Gurupi, it is imperative to conduct more comprehensive studies on the interactions among sand flies, Leishmania, and pathogen reservoirs in the area.

Spatial-temporal risk clusters, social vulnerability, and identification of priority areas for surveillance and control of cutaneous leishmaniasis in Maranhão, Brazil: an ecological study.

Cutaneous leishmaniasis (CL) is a neglected disease widely distributed in Maranhão, Brazil and presents a significant public health problem. However, its transmission dynamics and determining factors are not clearly understood. In this context, geospatial technologies help interpret the process. This study, then, characterized the space-time dynamics and the influence of social vulnerability on CL in an endemic area in Northeast Brazil. This is an ecological study about new cases of CL in Maranhão, from 2007 to 2020, obtained directly from the Notifiable Diseases Information System. The incidence rate was smoothed using a spatial empirical Bayesian method. Subsequently, global and local Moran statistics and their association with social vulnerability indicators were determined. Disease distribution was not random but grouped in space and time. All Social Vulnerability Index domains were positively correlated with the CL incidence. A likely cluster was detected in western Maranhão (P < 0.001), which encompassed 18 municipalities, from January 2007 to December 2013, with a high relative risk (5.06). The research findings suggest that planning public health actions and allocating resources should be prioritized in these areas to help effectively reduce the incidence of the disease.

M-shaped Genioplasty: New Findings after 10 Years of Experience.

This study aimed to evaluate changes of the M-shaped genioplasty in sagittal and vertical planes in a group of 34 patients and describe other indications, such as the increase of the mentolabial angle, decrease in the depth of the mentolabial fold, and the centering of the chin. Methods: A retrospective analysis was performed on 34 patients between 2010 and 2019. All studies were conducted at T0 (preoperative), T1 (a month after surgery), and T2 (1 year after surgery). The position of the bone pogonion (Pg) was measured vertically and horizontally at T0, T1, and T2; the mentolabial angle and the depth of the mentolabial fold were measured at T0 and T2. Results: The average sagittal advancement at T1 was 6.6 mm and at T2 was 6.4 mm. The inferior movement was an average of 5.6 mm at T1 and T2, showing both movements excellent stability. The mentolabial angle increased at T2 an average of 28.2 degrees (5 degrees per each millimeter of inferior movement), whereas the depth of the mentolabial fold decreased an average of 2.8 mm (decreased 49% from the initial depth and decreased 0.56 mm per each mm of inferior movement). The average increase of the lower third of the face was 5 mm. No complications were observed in any patient. Conclusions: M-shaped genioplasty is an anterior osteotomy of the mandible, which allows the chin to move forward and downward. Additionally, it allows an increase of the mentolabial angle and decreases the mentolabial fold.

Evaluation of the skin whitening and antioxidant activity of Myracrodruon urundeuva extract (aroeira-do-sertão).

Myracrodruon urundeuva, popularly known as 'aroeira-do-sertão', a large tree, with a tall trunk. Belonging to the Anacardiaceae family, it occurs in the 'caatinga' and dry forests of Brazil, from Ceará to the states of Paraná and Mato Grosso do Sul. The present study aimed to analyse the whitening and antioxidant activities of the aqueous extract of the leaves of Myracrodruon urundeuva (AELMU). Inhibition of the tyrosinase enzyme, as well as its copper chelating capacity and antioxidant effect were evaluated. The AELMU (at 2000 µg/mL) showed excellent inhibitory action (83.76%) on tyrosinase by chelating the copper ion while kojic acid at the same concentration inhibited 97.81%. Moreover, the extract displayed important antioxidant activity (inhibited 76,46% of the 2,2-diphenyl-1-picrylhydrazyl radical - DPPH; 49,59% of thiobarbituric acid reactive substances and 51,07% of the hydroxyl radical). Thus, the extract under study is promising for use in cosmetics, given its multifactorial action.

Spatiotemporal Distribution of Leishmaniasis in an Endemic Area of Northeast Brazil: Implications for Intervention Actions.

This study aimed to analyze the spatiotemporal distribution of leishmaniases, and contribute to the knowledge of their epidemiological dynamics from 2007 to 2017 in the municipality of Caxias, Maranhão, Northeast Brazil. Data on American tegumentary leishmaniasis (ATL) and human visceral leishmaniasis (HVL) were obtained in the Epidemiological Surveillance Sector of Caxias, while data on canine visceral leishmaniasis (CVL) were obtained in the Zoonoses Surveillance Unit. For data analysis and spatial representation of leishmaniasis cases, the geoprocessing of the data was performed, and the geometric features of the state of Maranhão, Caxias, and the disease registration sites were obtained from the shapefile database of the Brazilian Institute of Geography and Statistics. Geostatistics was used to create maps based on the Kernel density method, starting from the points, producing a raster file for each case with several data frames, allowing the instantaneous comparison of the phenomena. During the study period, ATL, HVL, and CVL were reported in Caxias, accounting for 114,304 and 8,498 cases, respectively. The geoprocessing analysis showed that leishmaniasis is widely distributed in the urban area of Caxias. However, there are risk areas for the transmission of these diseases to humans and dogs, associated with deforestation and urban expansion, and may vary over time. Preventive measures must focus on risk areas, including conservation efforts and urban planning, in order to reduce the transmission of leishmaniases.

Evaluation of participant satisfaction with community therapy: a mental health strategy in primary care.

Actions aimed at health promotion and disease prevention must prioritize the entry point to the health system. In this sense, it is proposed that Community Therapy (CT) be inserted as a mental health care tool in Primary Care. The purpose of this study is to assess user satisfaction with CT in Primary Care. It is assessment, cross-sectional study with a representative sample of users of CT services in Primary Care in the municipality of João Pessoa, Paraiba, Brazil. Of the 198 interviewees, 165 (83.3%) of the sample reported that they were always respected, evidenced by aspects of respect and dignity; 109 (55.1%) individuals stated they were listened to, revealing internal consistency of 0.7187, and in turn, exhibiting the true validity of the user satisfaction construct with respect to CT. Thus, users displayed positive satisfaction, reflected by respect, dignity, receptiveness, resolution, listening and comprehension received at CT, where empathy is exhibited and mental suffering is relieved. Moreover, CT is an important mental health tool in primary care.

[Social representations on aging by primary care health workers]. / Representações sociais de trabalhadores da atenção básica de saúde sobre envelhecimento.

The objective of this study was to get to know the social representations on aging developed by primary care health workers. This is an exploratory study involving 204 primary health care workers, in the city of João Pessoa, in the state of Paraíba. For data collection we used a semi-structured interview. The data obtained from 204 interviews was analyzed with the help of the Alceste software version 2010. The results indicated five classes or categories: vision of aging,psychosocial dimensions, a time of doubts, aging as a process, and aging versus disease, with positive content: joy, care, children, retirement, caregiver rights, maturity and wisdom, as well as negative factors: impairments, decadence, neglect, fragility, limitation, wrinkles, dependency and disease. It was observed that these meanings associated with aging express the need for total and humanized elderly care.

[Social representations of elders' quality of life]. / Representações sociais sobre qualidade de vida para idosos.

This study aimed to identify elders' social representations of quality of life. This is an exploratory study with a sample of 240 elders, of both sexes. For data collection we used a Free Association Test with Words, using the inductive stimulus 'quality of life" and sociodemographic variables. The interviews were analyzed with the software Alceste. Of the 240 studied eslders, 167 were women, with the dominant age from 60 to 69 years, income between two and three minimum wages, most of the married and with catholicism as the predominant religion. The results from Alceste pointed towards seven hierarchical classes: accessibility, work, activity, support affection, care and interactions. Social representations of quality of life by elders can support professionals in understanding the adhesion to preventive practices for the elderly and in strengthening policies directed to this population.

[Assessing the risk of falls for the elderly in Basic Health Units]. / Avaliação do risco de quedas em idosos atendidos em Unidade Básica de Saúde.

The world population is aging rapidly, which poses a greater challenge for the institutions involved which, in turn, require new public health policies that include the prevention of falls. The objective of this study was to assess the risk of falls in the elderly. This epidemiological, cross-sectional study was performed at a family health unit, using a quantitative approach. The sample consisted of 150 elderly individuals evaluated from January to April 2009. Data were collected using the Fall Risk Score, which was analyzed using SPSS 17.0. Of all seniors evaluated, 58.8% did not suffer falls. However, 63 seniors did suffer falls, 71.4% of this total experienced 1 to 2 falls, and the main intrinsic cause they reported was dizziness/vertigo, whereas the extrinsic cause was wet or slippery floors. Therefore, it is concluded that it is important to assess the risk of falls among the elderly so that preventive measures can be taken, with a view to maximizing their quality of life.

Blood pressure variability in individuals with diabetes mellitus: a scoping review.

OBJECTIVES: to map methods and devices used to assess very short-, short-, medium-, and long-term pressure variability in adults with type 1 or 2 diabetes mellitus. METHODS: scoping review conducted in January and February 2021 in MEDLINE, Web of Science, CINAHL, LILACS, PubMed, and Embase databases. Studies conducted within the last ten years analyzing pressure variability in adult and older patients with diabetes mellitus type 1 or 2 were included. Studies that used discontinued devices were excluded. RESULTS: the sample was composed of 25 articles published since 2017, with the majority developed in Japan (n=11); with the predominance of the oscillometric method (n=22); the most used devices were from the Omron® brand (n=14); the most detected type was long-term variability (n=10). CONCLUSIONS: we observed the increasing application of the oscillometric method for pressure variability analysis with various brands and models of automatic devices.