What are the main oral manifestations in heart transplant patients? A scoping review.

OBJECTIVE: The purpose of this scoping review is to evaluate the oral manifestations (OM) of heart transplant (HT) patients undergoing immunosuppressive therapy (IT). MATERIAL AND METHODS: A literature search was performed using keywords and MeSH terms related to OM and HT in the Medline/PubMed, Web of Science, Cochrane Library, Scopus, LILACS/BBO databases and in gray literature without language or date restrictions until June 2023. Studies that evaluated HT individuals who used any IT and who reported the occurrence of OM were considered eligible. The results from the search were imported to EndNote Web, and duplicates were removed followed by title/abstract and full-text analysis. RESULTS: A total of 402 nonduplicated studies were found and 13 fulfilled the criteria and were included in the present review: 10 cross-sectional, 2 cohorts, and 1 clinical trial. The most reported OM were periodontal diseases, including drug-induced gingival enlargement (DIGE), gingival bleeding, gingivitis, and periodontitis. Reported in a minority of studies are oral cancer, opportunistic infections (oral hairy leukoplakia and erythematous candidiasis), enamel defects, and burning mouth. CONCLUSION: Considering the methodological heterogeneity of the studies analyzed, DIGE is the most commonly observed oral manifestation in HT individuals.

Mapping the lipidome in mitochondria-associated membranes (MAMs) in an in vitro model of Alzheimer's disease.

The disruption of mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) plays a relevant role in Alzheimer's disease (AD). MAMs have been implicated in neuronal dysfunction and death since it is associated with impairment of functions regulated in this subcellular domain, including lipid synthesis and trafficking, mitochondria dysfunction, ER stress-induced unfolded protein response (UPR), apoptosis, and inflammation. Since MAMs play an important role in lipid metabolism, in this study we characterized and investigated the lipidome alterations at MAMs in comparison with other subcellular fractions, namely microsomes and mitochondria, using an in vitro model of AD, namely the mouse neuroblastoma cell line (N2A) over-expressing the APP familial Swedish mutation (APPswe) and the respective control (WT) cells. Phospholipids (PLs) and fatty acids (FAs) were isolated from the different subcellular fractions and analyzed by HILIC-LC-MS/MS and GC-MS, respectively. In this in vitro AD model, we observed a down-regulation in relative abundance of some phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and lysophosphatidylethanolamine (LPE) species with PUFA and few PC with saturated and long-chain FA. We also found an up-regulation of CL, and antioxidant alkyl acyl PL. Moreover, multivariate analysis indicated that each organelle has a specific lipid profile adaptation in N2A APPswe cells. In the FAs profile, we found an up-regulation of C16:0 in all subcellular fractions, a decrease of C18:0 levels in total fraction (TF) and microsomes fraction, and a down-regulation of 9-C18:1 was also found in mitochondria fraction in the AD model. Together, these results suggest that the over-expression of the familial APP Swedish mutation affects lipid homeostasis in MAMs and other subcellular fractions and supports the important role of lipids in AD physiopathology.

Zieve's Syndrome: An Underdiagnosed Cause of Non-immune Hemolytic Anemia.

Zieve's syndrome is an underdiagnosed condition characterized by the triad of jaundice, hemolytic anemia, and hyperlipidemia in the setting of chronic alcohol use. It may be accompanied by acute alcoholic hepatitis. The distinction between the coexistence of acute alcoholic hepatitis with Zieve's syndrome and Zieve's syndrome in isolation is crucial, given the different treatments and prognoses in these situations. A 35-year-old woman presented with complaints of abdominal discomfort, nausea, and vomiting in the previous week. She was a heavy drinker with resultant cirrhosis, splenomegaly, and esophageal varices. An ancillary test showed hemolytic anemia, moderately elevated transaminases, hyperbilirubinemia, and coagulopathy. A negative direct Coombs test established the anemia as non-immune, supporting the diagnosis of Zieve's syndrome despite the absence of hyperlipidemia. Maddrey's discriminant function score was 92 points, so she was treated with supportive measures, as well as corticosteroids in the setting of acute alcoholic hepatitis. The patient showed a favorable clinical and analytical evolution and was discharged home one month following admission with her hemoglobin levels stabilized. Previous literature focused on the distinction between Zieve's syndrome and acute alcoholic hepatitis but they may coexist.

Brazilian special olympics athletes: Oral health problems.

AIMS: The people with intellectual disabilities have been reported to be a vulnerable population in terms of oral health. This study was carried out to determine the oral health condition and treatment needs of Special Olympics athletes in Brazil. METHODS: This study is a retrospective review of oral health data collected from athletes participating in Healthy Athletes Program Special Olympics in Brazil, between the years 2015 and 2019. About 1241 athletes from the Brazil Special Olympics program were screened in the cities of São Paulo, Jundiai and Belo Horizonte (located in southeastern Brazil) and Recife (in northeastern Brazil). At each of these events, volunteer dental professionals performed an oral health screening for each athlete, All oral health assessments were done visually; and extra lighting were available if needed. The examinations were performed with the aid of a wooden spatula of the tongue depressor type and under natural light. The following parameters were recorded: mouth pain, untreated tooth decay, missing teeth, gingival signs, urgency and mouth hygiene habits. Data was analyzed using the STATA 14.0 program. Frequency tables were used for descriptive analyses. Categorical variables were compared between the different years of the event using the Chi-Square or Fisher's Exact test. Continuous variables were compared between different event years using the Kruskal-Wallis test followed by Dunn's post-hoc analyses. Simple logistic regression was used to assess the effect of age on dental assessment results. For all tests, a p-value was considered significant when less than or equal to .05. RESULTS: No statistically significant differences were observed in the frequencies of Mouth Pain and Missing Teeth over the years (p > .05). In relation to Untreated Tooth Decay, there is a higher frequency in the years 2016 and 2018 and a lower frequency in the year 2015 (p = .048). Regarding Gingival Signs of inflammation, there is a higher frequency in the years 2016 and 2018 and a lower frequency in the year 2017 (p < .001). In relation to cases of urgency (in need of treatment (Urgent treatment need, Non-Urgent or Maintenance)), there was a higher frequency (no urgency) in 2016 (p = .007). Finally, in relation to mouth hygiene habits, there is a higher frequency of participants with irregular habits in the years 2017 and 2019 (p < .001). CONCLUSION: The dental condition of Brazilian athletes Special Olympycs Brazil reported in this study from 2015 to 2019 showed us that athletes have a high prevalence of dental diseases and these needs could contribute to health damage. The athletes have many unmet dental treatment needs and these needs are similar in different regions of the country and in the years reported.

Are tomato plants co-exposed to heat and salinity able to ensure a proper carbon metabolism? - An insight into the photosynthetic hub.

Abiotic stress combinations, such as high temperatures and soil/water salinization, severely threaten crop productivity worldwide. In this work, an integrative insight into the photosynthetic metabolism of tomato plants subjected to salt (100 mM NaCl) and/or heat (42 °C; 4 h/day) was performed. After three weeks, the stress combination led to more severe consequences on growth and photosynthetic pigments than the individual stresses. Regarding the photochemical efficiency, transcript accumulation and protein content of major actors (CP47 and D1) were depleted in all stressed plants, although the overall photochemical yield was not negatively affected under the co-exposure. Gas-exchange studies revealed to be mostly affected by salt (single or combined), which harshly compromised carbon assimilation. Additionally, transcript levels of stress-responsive genes (e.g., HsfA1 and NHX2) were differentially modulated by the single and combined treatments, suggesting the activation of stress-signature responses. Overall, by gathering an insightful overview of the main regulatory hub of photosynthesis, we show that the impacts on the carbon metabolism coming from the combination of heat and salinity, two major conditioners of crop yields, were not harsher than those of single stresses, indicating that the growth impairment might be attributed to a proficient distribution of resources towards defense mechanisms.

Validation and Cultural Adaptation of the Problem Areas in Diabetes-5 (PAID-5) Scale to European Portuguese.

INTRODUCTION: Diabetes distress syndrome (DDS) can lead to poor outcomes and should be assessed with adapted and validated tools. One of these tools is the Problem Areas in Diabetes (PAID) scale, which assesses diabetes distress in people suffering from diabetes (PsD). A short five-item form, PAID-5, is an easier and quicker alternative to be used in clinical and research practices, than the previous one with 20-items and has been validated by the original authors. This study intended to perform the cultural adaptation and validation of the PAID-5 scale in European Portuguese. METHODS: To create the Portuguese version of PAID-5, translation-back translation, a clinical review, and a cognitive debriefing panel were performed. A convenience sample of 90 PsD was studied in three primary healthcare units for reliability and validity tests. Reliability was studied by the internal consistency (Cronbach's alpha) and the interval coefficient correlation (ICC) under a test-retest design. Structural validity was studied by principal component analysis. The construct validity was tested by the sensitivity of the PAID-5 total score with age, most recent HbA1c test, and socioeconomic class by the Socio-Economic Deprivation Index (SEDI). Criterion validity was tested by correlating the PAID-5 total score with the psychological distress questions of the Diabetes Health Profile 18 Questions (DHP-PDQ). RESULTS: A Cronbach's alpha coefficient value of 0.905 and an ICC of 0.905 were computed. In a sample of n = 90 PsD, 55.6% were males, 63.3% aged 65 years or more, SEDI was 5.2 ± 0.8 [3 to 6], 44.4% studied for less than 4 years, and 18.9% were living alone. The Spearman correlation between PAID-5 and DHP-PDQ total scores was ρ = 0.382, p < 0.001, between PAID-5 total score and age was ρ = -0.207, p = 0.050 and between PAID-5 total score and most recent HbA1c knowledge was ρ = 0.275, p = 0.040. There was no significant relationship between PAID-5 total score and SEDI ρ = 0.080, p = 0.452. CONCLUSION: DDS can now be assessed in the Portuguese context, accounting for better intervention by primary care teams. PAID-5 has good psychometric properties and is a reliable scale to identify diabetes-specific distress in the Portuguese diabetic population.

PI3K signaling promotes formation of lipid-laden foamy macrophages at the spinal cord injury site.

After spinal cord injury (SCI), infiltrating macrophages undergo excessive phagocytosis of myelin and cellular debris, forming lipid-laden foamy macrophages. To understand their role in the cellular pathology of SCI, investigation of the foamy macrophage phenotype in vitro revealed a pro-inflammatory profile, increased reactive oxygen species (ROS) production, and mitochondrial dysfunction. Bioinformatic analysis identified PI3K as a regulator of inflammation in foamy macrophages, and inhibition of this pathway decreased their lipid content, inflammatory cytokines, and ROS production. Macrophage-specific inhibition of PI3K using liposomes significantly decreased foamy macrophages at the injury site after a mid-thoracic contusive SCI in mice. RNA sequencing and in vitro analysis of foamy macrophages revealed increased autophagy and decreased phagocytosis after PI3K inhibition as potential mechanisms for reduced lipid accumulation. Together, our data suggest that the formation of pro-inflammatory foamy macrophages after SCI is due to the activation of PI3K signaling, which increases phagocytosis and decreases autophagy.

Biosensors for natriuretic peptides in cardiovascular diseases. A review.

Heart failure (HF) is a complex clinical syndrome associated with high rates of morbidity and mortality. Over the years, it has been crucial to find accurate biomarkers capable of doing a precise monitor of HF and provide an early diagnosis. Of these, it has been established an important role of natriuretic peptides in HF assessment. Moreover, the development of biosensors has been garnering interest as new diagnostic medical tools. In this review we first provide a general overview of HF, its pathogenesis, and diagnostic features. We then discuss the role of natriuretic peptides in heart failure by characterizing them and point out their potential as biomarkers. Finally, we adress the evolution of biosensors development and the available natriuretic peptides biosensors for disease monitoring.

Effect of Ferulago lutea (Poir.) Grande Essential Oil on Molecular Hallmarks of Skin Aging.

With the increase in global life expectancy, maintaining health into old age becomes a challenge, and research has thus concentrated on various strategies which aimed to mitigate the effects of skin aging. Aromatic plants stand out as promising sources of anti-aging compounds due to their secondary metabolites, particularly essential oils (EOs). The aim of this study was to ascribe to Ferulago lutea EO several biological activities that could be useful in the context of skin aging. The EO was obtained using hydrodistillation and characterized by gas chromatography-mass spectrometry (GC/MS). The anti-inflammatory potential was assessed using lipopolysaccharide (LPS)-stimulated macrophages. The effect on cell migration was disclosed using scratch wound assay. Lipogenesis was induced using T0901317, hyperpigmentation with 3-isobutyl-1-methylxantine (IBMX) and senescence with etoposide. Our results show that the EO was characterized mainly by α-pinene and limonene. The EO was able to decrease nitric oxide (NO) release as well as iNOS and pro-IL-1ß protein levels. The EO promoted wound healing while decreasing lipogenesis and having depigmenting effects. The EO also reduced senescence-associated ß-galactosidase, p21/p53 protein levels and the nuclear accumulation of γH2AX. Overall, our study highlights the properties of F. lutea EO that make it a compelling candidate for dermocosmetics applications.

COVID-19 inpatient mortality in Brazil from 2020 to 2022: a cross-sectional overview study based on secondary data.

BACKGROUND: In Brazil, the COVID-19 pandemic found the universal and public Unified Health System (SUS) with problems accumulated over time, due, among other reasons, to low investments, and disparities in resource distribution. The preparedness and response of the healthcare system, involving the SUS and a private sector, was affected by large socioeconomic and healthcare access inequities. This work was aimed at offering an overview of COVID-19 inpatient mortality during the pandemic in Brazil, exploring factors associated with its variations and, specifically, differences across public, private (for-profit) and philanthropic (private non-profit) inpatient healthcare units, providers, and non-providers of services to the SUS. METHODS: This cross-sectional study used public secondary data. The main data source was the SIVEP-Gripe, which comprises data on severe acute respiratory illness records prospectively collected. We also employed the National Record of Health Establishments, the SUS' Hospitalization Information System and municipalities' data from IBGE. We considered adult COVID-19 hospitalizations registered in SIVEP-Gripe from February 2020 to December 2022 in inpatient healthcare units with a minimum of 100 cases in the period. Data analyses explored the occurrence of inpatient mortality, employing general linear mixed models to identify the effects of patients', health care processes', healthcare units' and municipalities' characteristics on it. RESULTS: About 70% of the COVID-19 hospitalizations in Brazil were covered by the SUS, which attended the more vulnerable population groups and had worse inpatient mortality. In general, non-SUS private and philanthropic hospitals, mostly reimbursed by healthcare insurance plans accessible for more privileged socioeconomic classes, presented the best outcomes. Southern Brazil had the best performance among the macro-regions. Black and indigenous individuals, residents of lower HDI municipalities, and those hospitalized out of their residence city presented higher odds of inpatient mortality. Moreover, adjusted inpatient mortality rates were higher in the pandemic peak moments and were significantly reduced after COVID-19 vaccination reaching a reasonable coverage, from July 2021. CONCLUSIONS: COVID-19 exposed socioeconomic and healthcare inequalities and the importance and weaknesses of SUS in Brazil. This work indicates the need to revert the disinvestment in the universal public system, a fundamental policy for reduction of inequities in the country.

Epidural Anesthesia for Cesarean Section in a Pregnant Woman With Acute Pulmonary Edema: A Case Report.

Although rare, acute pulmonary edema is the most common cause of death in pregnant women with severe hypertension. The authors report a case involving a pregnant woman at 36 weeks of gestation with preeclampsia, who exhibited pulmonary edema and required immediate cesarean delivery. The patient had type 1 respiratory failure and needed supplemental oxygenation with a Venturi mask. The cesarean section was performed successfully under epidural anesthesia. Women with severe preeclampsia and acute pulmonary edema remain a challenge when presented for cesarean delivery, and the best anesthetic option remains controversial.

Unveiling the efficacy of pre-emergent application of young Eucalyptus globulus leaves as a weed control strategy: Bridging macroscopic effects and cellular responses.

Allelopathy, the inhibition of neighbouring plant growth by certain plants, can be particularly useful if applied in a targeted way for weed management. So, this study aimed to assess and characterize the herbicidal activity of fresh and dried leaves from young Eucalyptus globulus Labill. trees applied as a soil amendment. For this, fresh and dried leaves (FL and DL, respectively) were incorporated into the soil at different concentrations (0, 1, 5, and 10% w/w), where Portulaca oleracea L. seeds were sown. After 5 weeks of exposure, results revealed that the soil incorporation of DL at 10% (w/w) presented the strongest herbicidal properties, inhibiting seed germination by 63% and inducing the loss of cell viability. To unravel the possible mode of action and the main targets at both cellular and subcellular levels, an in vitro experiment was performed. Purslane seeds were sown in a nutritive medium containing different dilutions of an aqueous extract prepared with dried eucalyptus leaves. After 5 days of exposure, germinated seedlings were processed for transmission electron microscopy and histological analyses as well as for reactive oxygen species (ROS) in vivo detection by confocal laser scanning microscopy. Results revealed that the allelochemical release from DL induced ROS overproduction, resulting in the loss of cell integrity and organization, which was characterized by damage to several cellular sub-structures, along with enhanced accumulation of lipid droplets. Overall, the incorporation of DL into the soil can represent a sustainable alternative to reduce synthetic herbicide application and subsequent environmental contamination.

The journey of cardosin A in young Arabidopsis seedlings leads to evidence of a Golgi-independent pathway to the protein storage vacuole.

The aspartic proteinase cardosin A is a vacuolar enzyme found to accumulate in protein storage and lytic vacuoles in the flowers and protein bodies in the seeds of the native plant cardoon. Cardosin A was first isolated several decades ago and has since been extensively characterized, both in terms of tissue distribution and enzyme biochemistry. In the native system, several roles have been attributed to cardosin A, such as reproduction, reserve mobilization, and membrane remodeling. To participate in such diverse events, cardosin A must accumulate and travel to different compartments within the cell: protein storage vacuoles, lytic vacuoles, and the cytoplasmic membrane (and eventually outside the cell). Several studies have approached the expression of cardosin A in Arabidopsis thaliana and Nicotiana tabacum with promising results for the use of these systems to study of cardosin A trafficking. A poly-sorting mechanism has been uncovered for this protein, as two different vacuolar sorting determinants, mediating different vacuolar routes, have been described. The first is a conventional C-terminal domain, which delivers the protein to the vacuole via the Golgi, and the second is a more unconventional signal-the plant-specific insert (PSI)-that mediates a Golgi-independent route. The hypothesis that these two signals are activated according to cell needs and in organs with high metabolic activity is investigated here. An Arabidopsis line expressing cardosin A under an inducible promoter was used to understand the dynamics of cardosin A regarding vacuolar accumulation during seed germination events. Using antibodies against different regions of the protein and combining them with immunofluorescence and immunocytochemistry assays in different young seedling tissues, cardosin A was detected along the secretory pathway to the protein storage vacuole, often associated with the endoplasmic reticulum. More interestingly, upon treatment with the drug Brefeldin A, cardosin A was still detected in protein storage vacuoles, indicating that the intact protein can bypass the Golgi in this system, contrary to what was observed in N. tabacum. This study is a good starting point for further research involving the use of fluorescent fusions and exploring in more detail the relationship between cardosin A trafficking and plant development.

Problemas ligados ao álcool em centros de emergência (PLACE)-People experiencing homelessness with alcohol-related problems in Lisbon's emergency shelters during the COVID-19 pandemic: a description and analysis of a harm reduction intervention.

Introduction: Alcohol-related problems disproportionally affect people experiencing homelessness. As the first wave of the COVID-2019 pandemic spread in 2020, a number of emergency shelters were opened in Lisbon. Increased difficulties in obtaining alcohol could have led to an increased incidence of alcohol withdrawal. Therefore, a low-threshold harm reduction intervention was introduced to these emergency shelters. This consisted of a fixed medication treatment, made available immediately for those with specific conditions, without the need for a medical evaluation or abstinence from alcohol, together with an offer of subsequent access to specialized addiction centers. The Problemas Ligados ao Álcool em Centros de Emergência (PLACE) study (alcohol-related problems in emergency shelters) is a retrospective mixed-methods observational study. It describes the demographic, health, and social characteristics of shelter users participating in the program and aims to evaluate the intervention as well as the experience of the patients, professionals, and decision-makers involved. Results: A total of 69 people using shelters self-reported alcohol-related problems. Among them, 36.2% of the people accepted a pharmacological intervention, and 23.2% selected an addiction appointment. The take-up of the intervention was associated with better housing outcomes. A description of an individual's trajectory after leaving the shelter is provided. Discussion: This study suggests that non-abstinence-focused interventions can be useful and well-tolerated in treating addiction in this population.

CCL21-CCR7 signaling promotes microglia/macrophage recruitment and chemotherapy resistance in glioblastoma.

Glioblastoma (GBM) is the most common and fatal primary tumor of the central nervous system (CNS) and current treatments have limited success. Chemokine signaling regulates both malignant cells and stromal cells of the tumor microenvironment (TME), constituting a potential therapeutic target against brain cancers. Here, we investigated the C-C chemokine receptor type 7 (CCR7) and the chemokine (C-C-motif) ligand 21 (CCL21) for their expression and function in human GBM and then assessed their therapeutic potential in preclinical mouse GBM models. In GBM patients, CCR7 expression positively associated with a poor survival. CCL21-CCR7 signaling was shown to regulate tumor cell migration and proliferation while also controlling tumor associated microglia/macrophage recruitment and VEGF-A production, thereby controlling vascular dysmorphia. Inhibition of CCL21-CCR7 signaling led to an increased sensitivity to temozolomide-induced tumor cell death. Collectively, our data indicate that drug targeting of CCL21-CCR7 signaling in tumor and TME cells is a therapeutic option against GBM.

Conceptual framework for management or transmission of knowledge in companies: A systematic review.

The literature on knowledge management as a broad area, typically studied under the scope of business management, and on knowledge transmission as a process, often studied under the scope of work psychology and ergonomics, although extensive, lacks a synthesis regarding the dimensions involved in knowledge management or transmission practices in workplaces. Thus, this study aims to systematize the existing programs for management or transmission of knowledge in workplaces and to develop a conceptual framework to support their design and implementation in this context. Thereto, the study resorts to the main scientific approaches that address knowledge management and knowledge transmission (business management and work psychology/ergonomics). The methodology followed a systematic review to identify and analyse the programs concerning the management or transmission of knowledge implemented in professional contexts, nearly from the beginning of the 21st century, considering the two scientific approaches. The analysis of the 28 articles shows what defines the implemented practices, their impact, and the role assumed by HR. The results demonstrate differences and similarities between the two approaches which guided the dimensions included in the conceptual framework. This study makes advances for both the scientific field, bringing different scientific discourses closer together by acknowledging their strengths; and for practitioners, through the possibility of improving the understanding of the application scope of the concepts of knowledge management and knowledge transmission, as well as supporting their action in workplaces.

Exploiting the Integrated Valorization of Eucalyptus globulus Leaves: Chemical Composition and Biological Potential of the Lipophilic Fraction before and after Hydrodistillation.

E. globulus leaves have been mainly exploited for essential oil recovery or for energy generation in industrial pulp mills, neglecting the abundance of valuable families of extractives, namely, triterpenic acids, that might open new ways for the integrated valorization of this biomass. Therefore, this study highlights the lipophilic characterization of E. globulus leaves before and after hydrodistillation, aiming at the integrated valorization of both essential oils and triterpenic acids. The lipophilic composition of E. globulus leaves after hydrodistillation is reported for the first time. Extracts were obtained by dichloromethane Soxhlet extraction and analyzed by gas chromatography-mass spectrometry. In addition, their cytotoxicity on different cell lines representative of the innate immune system, skin, liver, and intestine were evaluated. Triterpenic acids, such as betulonic, oleanolic, betulinic and ursolic acids, were found to be the main components of these lipophilic extracts, ranging from 30.63-37.14 g kg-1 of dry weight (dw), and representing 87.7-89.0% w/w of the total content of the identified compounds. In particular, ursolic acid was the major constituent of all extracts, representing 46.8-50.7% w/w of the total content of the identified compounds. Other constituents, such as fatty acids, long-chain aliphatic alcohols and ß-sitosterol were also found in smaller amounts in the studied extracts. This study also demonstrates that the hydrodistillation process does not affect the recovery of compounds of greatest interest, namely, triterpenic acids. Therefore, the results establish that this biomass residue can be considered as a promising source of value-added bioactive compounds, opening new strategies for upgrading pulp industry residues within an integrated biorefinery context.

A Perspective on the Link between Mitochondria-Associated Membranes (MAMs) and Lipid Droplets Metabolism in Neurodegenerative Diseases.

Mitochondria interact with the endoplasmic reticulum (ER) through contacts called mitochondria-associated membranes (MAMs), which control several processes, such as the ER stress response, mitochondrial and ER dynamics, inflammation, apoptosis, and autophagy. MAMs represent an important platform for transport of non-vesicular phospholipids and cholesterol. Therefore, this region is highly enriched in proteins involved in lipid metabolism, including the enzymes that catalyze esterification of cholesterol into cholesteryl esters (CE) and synthesis of triacylglycerols (TAG) from fatty acids (FAs), which are then stored in lipid droplets (LDs). LDs, through contact with other organelles, prevent the toxic consequences of accumulation of unesterified (free) lipids, including lipotoxicity and oxidative stress, and serve as lipid reservoirs that can be used under multiple metabolic and physiological conditions. The LDs break down by autophagy releases of stored lipids for energy production and synthesis of membrane components and other macromolecules. Pathological lipid deposition and autophagy disruption have both been reported to occur in several neurodegenerative diseases, supporting that lipid metabolism alterations are major players in neurodegeneration. In this review, we discuss the current understanding of MAMs structure and function, focusing on their roles in lipid metabolism and the importance of autophagy in LDs metabolism, as well as the changes that occur in neurogenerative diseases.

Preferences for pre-exposure prophylaxis (PrEP) among sexual and gender minorities: a discrete choice experiment in Brazil.

Background: Men who have sex with men (MSM) and transgender women (TGW) are disproportionally affected by HIV infection in Latin America. This study aims to assess pre-exposure prophylaxis (PrEP) preferences among sexual and gender minorities (SGM) and identify attributes and levels that are related to PrEP uptake and adherence, both crucial for PrEP success. Methods: We conducted a discrete choice experiment (DCE) among SGM from all Brazilian regions (September-December/2020). The survey was administered face-to-face (five Brazilian capitals) and online (entire country). We used a D-efficient zero-prior blocked experimental design to select 60 paired-profile DCE choice tasks. Findings: The total sample size was 3924 (90.5% MSM; 7.2% TGW and 2.3% non-binary or gender diverse persons). In random-effects logit models, highest levels of protection and "no side effects" were the most important attribute levels. For "presentation", injectable and implant were preferred over oral. Participants were willing to accept a 4.1% protection reduction to receive injectable PrEP or a 4.2% reduction if PrEP were taken monthly. The largest class in the latent class models was defined predominantly by the preference for the highest HIV protection level (p < 0.005). Respondents in this class also preferred no side effects, injectable and implant presentations. Interpretation: Higher HIV protection, no side effects, and presentation, whether injectable or implant, were the most important attributes in PrEP preferences. Protection against HIV was the most important attribute. PrEP programs should make available technologies such as long-acting presentations that could reunite the most desired attributes, thus maximizing acceptability and user-appropriateness. Funding: Unitaid.