Measuring Replicative Lifespan in Cryptococcus neoformans.

Advances in understanding cellular aging research have been possible due to the analysis of the replicative lifespan of yeast cells. Studying longevity in the pathogenic yeast Cryptococcus neoformans is essential because old yeast cells with age-related phenotypes accumulate during infection and are associated with increased virulence and antifungal tolerance. Microdissection and microfluidic devices are valuable tools for continuously tracking cells at the single-cell level. In this chapter, we describe the features of these two platforms and outline technical limitations and information to study aging mechanisms while assessing the lifespan of yeast cells.

Listeria monocytogenes from Food Products and Food Associated Environments: Antimicrobial Resistance, Genetic Clustering and Biofilm Insights.

Listeria monocytogenes, a foodborne pathogen, exhibits high adaptability to adverse environmental conditions and is common in the food industry, especially in ready-to-eat foods. L. monocytogenes strains pose food safety challenges due to their ability to form biofilms, increased resistance to disinfectants, and long-term persistence in the environment. The aim of this study was to evaluate the presence and genetic diversity of L. monocytogenes in food and related environmental products collected from 2014 to 2022 and assess antibiotic susceptibility and biofilm formation abilities. L. monocytogenes was identified in 13 out of the 227 (6%) of samples, 7 from food products (meat preparation, cheeses, and raw milk) and 6 from food-processing environments (slaughterhouse-floor and catering establishments). All isolates exhibited high biofilm-forming capacity and antibiotic susceptibility testing showed resistance to several classes of antibiotics, especially trimethoprim-sulfamethoxazole and erythromycin. Genotyping and core-genome clustering identified eight sequence types and a cluster of three very closely related ST3 isolates (all from food), suggesting a common contamination source. Whole-genome sequencing (WGS) analysis revealed resistance genes conferring resistance to fosfomycin (fosX), lincosamides (lin), fluoroquinolones (norB), and tetracycline (tetM). In addition, the qacJ gene was also detected, conferring resistance to disinfecting agents and antiseptics. Virulence gene profiling revealed the presence of 92 associated genes associated with pathogenicity, adherence, and persistence. These findings underscore the presence of L. monocytogenes strains in food products and food-associated environments, demonstrating a high virulence of these strains associated with resistance genes to antibiotics, but also to disinfectants and antiseptics. Moreover, they emphasize the need for continuous surveillance, effective risk assessment, and rigorous control measures to minimize the public health risks associated to severe infections, particularly listeriosis outbreaks. A better understanding of the complex dynamics of pathogens in food products and their associated environments can help improve overall food safety and develop more effective strategies to prevent severe health consequences and economic losses.

Resistome, Virulome, and Clonal Variation in Methicillin-Resistant Staphylococcus aureus (MRSA) in Healthy Swine Populations: A Cross-Sectional Study.

This cross-sectional study investigates the methicillin-resistant Staphylococcus aureus (MRSA): its prevalence, antimicrobial resistance, and molecular characteristics in healthy swine populations in central Portugal. A total of 213 samples were collected from pigs on twelve farms, and MRSA prevalence was assessed using selective agar plates and confirmed via molecular methods. Antimicrobial susceptibility testing and whole genome sequencing (WGS) were performed to characterize resistance profiles and genetic determinants. Among the 107 MRSA-positive samples (83.1% prevalence), fattening pigs and breeding sows exhibited notably high carriage rates. The genome of 20 isolates revealed the predominance of the ST398 clonal complex, with diverse spa types identified. Antimicrobial susceptibility testing demonstrated resistance to multiple antimicrobial agents, including penicillin, cefoxitin, and tetracycline. WGS analysis identified a diverse array of resistance genes, highlighting the genetic basis of antimicrobial resistance. Moreover, virulence gene profiling revealed the presence of genes associated with pathogenicity. These findings underscore the significant prevalence of MRSA in swine populations and emphasize the need for enhanced surveillance and control measures to mitigate zoonotic transmission risks. Implementation of prudent antimicrobial use practices and targeted intervention strategies is essential to reducing MRSA prevalence and safeguarding public health. Continued research efforts are warranted to elucidate transmission dynamics and virulence potential, ultimately ensuring food safety and public health protection.

Changes in Astroglial Water Flow in the Pre-amyloid Phase of the STZ Model of AD Dementia.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease that is typically sporadic and has a high social and economic cost. We utilized the intracerebroventricular administration of streptozotocin (STZ), an established preclinical model for sporadic AD, to investigate hippocampal astroglial changes during the first 4 weeks post-STZ, a period during which amyloid deposition has yet to occur. Astroglial proteins aquaporin 4 (AQP-4) and connexin-43 (Cx-43) were evaluated, as well as claudins, which are tight junction (TJ) proteins in brain barriers, to try to identify changes in the glymphatic system and brain barrier during the pre-amyloid phase. Glial commitment, glucose hypometabolism and cognitive impairment were characterized during this phase. Astroglial involvement was confirmed by an increase in glial fibrillary acidic protein (GFAP); concurrent proteolysis was also observed, possibly mediated by calpain. Levels of AQP-4 and Cx-43 were elevated in the fourth week post-STZ, possibly accelerating the clearance of extracellular proteins, since these proteins actively participate in the glymphatic system. Moreover, although we did not see a functional disruption of the blood-brain barrier (BBB) at this time, claudin 5 (present in the TJ of the BBB) and claudin 2 (present in the TJ of the blood-cerebrospinal fluid barrier) were reduced. Taken together, data support a role for astrocytes in STZ brain damage, and suggest that astroglial dysfunction accompanies or precedes neuronal damage in AD.

Resilience among organ donation coordinators: a Canadian mixed-methods study.

Background: Organ and Tissue Donation Coordinators (OTDCs) are key to the success of deceased organ donation processes. However, reduced resilience can leave them susceptible to the incidence of work-related issues and decrease the quality of the care provided. Therefore, this study aimed to examine the extent of resilience and influencing aspects among OTDCs in Canada. Methods: Mixed-method (QUAN-qual) explanatory sequential design. Quantitative data was collected using an online cross-sectional survey approach with demographic data and the validated scales and analyzed using descriptive and inferential statistics. Qualitative data was collected using a descriptive approach with a semi-structured interview guide and analyzed using content analysis. Results: One hundred twenty participants responded to the survey, and 39 participants were interviewed. Most participants from the survey were female (82%), registered nurses (97%) and on average 42 years old. The quantitative data revealed that OTDCs had a high level of perceived compassion satisfaction (ProQOL-CS = 36.3) but a resilience score (CD-RISC = 28.5) lower than other groups of healthcare professionals. OTDCs with over a year of experience in the role were more likely to have higher levels of resilience. The qualitative data identified that participants saw resilience as crucial for their work-related well-being. Although coping strategies were identified as a key factor that enhance resilience, many OTDCs reported difficulty in developing healthy coping strategies, and that the use of unhealthy mechanisms (e.g., alcohol and smoking) can result in negative physical consequences (e.g., weight gain) and reduced resilience levels. Conclusion: Participants reported using a series of coping and protective strategies to help build resilience, but also difficulty in developing healthy mechanisms. The lack of healthy coping strategies were seen as contributing to negative work-related issues (e.g., burnout). Our findings are being used to develop tailored interventions to improve resilience and healthy coping strategies among organ donor coordinators in Canada.

Plasma ADAM10 Levels and Their Association with Alzheimer's Disease Diagnosis in Older Adults with Fewer Years of Formal Education.

INTRODUCTION: Low educational attainment is a potential risk factor for Alzheimer's disease (AD) development. Alpha-secretase ADAM10 plays a central role in AD pathology, attenuating the formation of beta-amyloid peptides and, therefore, their aggregation into senile plaques. This study seeks to investigate ADAM10 as a blood-based biomarker in mild cognitive impairment (MCI) and AD in a diverse group of community-dwelling older adults, focusing on those with limited educational attainment. METHODS: Participants were recruited from public health services. Cognition was evaluated using Mini-Mental State Examination (MMSE) and Addenbrooke's Cognitive Examination - Revised (ACE-R) batteries. Blood samples were collected to analyze plasma ADAM10 levels. A logistic regression was conducted to verify the influence of plasma ADAM10 on the AD diagnosis. RESULTS: Significant differences in age, years of education, prescribed medications, and cognitive test scores were found between the MCI and AD groups. Regarding cognitive performance, both ACE-R and MMSE scores displayed significant differences between groups, with post hoc analyses highlighting these distinctions, particularly between AD and cognitively unimpaired individuals. Elevated plasma ADAM10 levels were associated with a 4.5-fold increase in the likelihood of a diagnosis of MCI and a 5.9-fold increase in the likelihood of a diagnosis of AD. These findings suggest ADAM10 levels in plasma as a valuable biomarker for assessing cognitive status in older individuals with low education attainment. CONCLUSION: This study underscores the potential utility of plasma ADAM10 levels as a blood-based biomarker for cognitive status, especially in individuals with low educational backgrounds, shedding light on their relevance in AD development and diagnosis.

Evaluation of calcium hydroxide mixed with propolis by ultrasonic activation as root canal dressing in delayed tooth replantation.

Background: In cases of tooth avulsion, in which the neurovascular bundle responsible for nourishing the dental pulp is break, endodontic treatment is necessary before proceeding with tooth replantation. In this process, various substances have been tested in combination with calcium hydroxide Ca(OH)2 in an attempt to improve its effectiveness. This study aimed to examine the effects of using a mixture of Ca(OH)2 and 10% propolis, with subsequent application of ultrasonic treatment, on the delayed replantation of teeth in rats. Material and Methods: Twenty-four rats underwent a surgical procedure to extract the upper right incisor, leaving it on a surface to dry for one hour. The pulp and periodontal ligament were removed and the teeth were submerged in a 2% sodium fluoride acidulated phosphate solution. The canals were dehydrated using paper cones and the teeth were divided into four groups, according to the type of intracanal dressing: Ca(OH)2 group, Ca(OH)2 group with ultrasonic agitation, Ca(OH)2 and propolis group, Ca(OH)2 and propolis group with ultrasonic agitation. The root canals were irrigated with saline solution and the teeth were reimplanted. Sixty days after reimplantation, the animals were euthanized. Results: With regard to the presence of acute and chronic inflammatory infiltrate in the periodontal ligament, there was no statistically significant difference among some of the groups. Root resorption was identified in all groups, and there was no significant difference between them. Conclusions: It is concluded that the application of intracanal dressing containing Ca(OH)2 associated with 10% propolis, followed by ultrasonic agitation, did not prove to be more effective than the use of Ca(OH)2 alone in the repair process in the delayed replantation of rat teeth. Key words:Tooth replantation, Calcium hydroxide, Propolis, Ultrasound, Intracanal dressing.

Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats.

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

Effect of metformin in hypothalamic astrocytes from an immunocompromised mice model.

Astrocytes are glial cells that play key roles in neuroinflammation, which is a common feature in diabetic encephalopathy and aging process. Metformin is an antidiabetic compound that shows neuroprotective properties, including in inflammatory models, but astroglial signaling pathways involved are still poorly known. Interferons α/ß are cytokines that participate in antiviral responses and the lack of their signaling increases susceptible to viral infections. Here, we investigated the effects of metformin on astrocytes from hypothalamus, a crucial brain region related to inflammatory processes. Astrocyte cultures were derived from interferon α/ß receptor knockout (IFNα/ßR-/-) and wild-type (WT) mice. Metformin did not change the expression of glial fibrillary acidic protein but caused an anti-inflammatory effect by decreasing pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1ß), as well as increasing gene expression of anti-inflammatory proteins interleukin-10 and Nrf2 (nuclear factor erythroid derived 2 like 2). However, nuclear factor κB p65 and cyclooxygenase 2 were downregulated in WT astrocytes and upregulated in IFNα/ßR-/- astrocytes. AMP-activated protein kinase (AMPK), a molecular target of metformin, was upregulated only in WT astrocytes, while sirtuin 1 increased in both mice models. The expression of inducible nitric oxide synthase was decreased in WT astrocytes and heme oxygenase 1 was increased in IFNα/ßR-/- astrocytes. Although loss of IFNα/ßR-mediated signaling affects some effects of metformin, our results support beneficial roles of this drug in hypothalamic astrocytes. Moreover, paradoxical response of metformin may involve AMPK. Thus, metformin can mediate glioprotection due its effects on age-related disorders in non-diabetic and diabetic encephalopathy individuals.

Rabbits as a Reservoir of Multidrug-Resistant Escherichia coli: Clonal Lineages and Public Health Impact.

Escherichia coli, including extended-spectrum ß-lactamases (ESBL)-producing strains, poses a global health threat due to multidrug resistance, compromising food safety and environmental integrity. In industrial settings, rabbits raised for meat have the highest consumption of antimicrobial agents compared to other food-producing animals. The European Union is facing challenges in rabbit farming as rabbit consumption declines and antibiotic-resistant strains of E. coli cause enteric diseases. The aim of this study was to investigate the antibiotic resistance profile, genetic diversity, and biofilm formation in cefotaxime-resistant E. coli strains isolated from twenty rabbit farms in Northern Portugal to address the effect of the pressing issue of antibiotic resistance in the rabbit farming industry. Resistance to critically antibiotics was observed, with high levels of resistance to several categories, such as tetracycline, ampicillin, aztreonam, and streptomycin. However, all isolates were susceptible to cefoxitin and imipenem. Multidrug resistance was common, with strains showing resistance to all antibiotics tested. The blaCTX-M variants (blaCTX-3G and blaCTX-M9), followed by the tetracycline resistance genes, were the most frequent resistance genes found. ST10 clones exhibiting significant resistance to various categories of antibiotics and harboring different resistance genes were detected. ST457 and ST2325 were important sequence types due to their association with ESBL-E. coli isolates and have been widely distributed in a variety of environments and host species. The strains evaluated showed a high capacity for biofilm formation, which varied when they were grouped by the number of classes of antibiotics to which they showed resistance (i.e., seven different classes of antibiotics, six classes of antibiotics, and three/four/five classes of antibiotics). The One Health approach integrates efforts to combat antimicrobial resistance in rabbit farming through interdisciplinary collaboration of human, animal, and environmental health. Our findings are worrisome and raise concerns. The extensive usage of antibiotics in rabbit farming emphasizes the urgent need to establish active surveillance systems.

Host-Pathogen Interactions and Correlated Factors That Are Affected in Replicative-Aged Cryptococcus neoformans.

Cryptococcus neoformans is a facultative intracellular fungal pathogen. Ten-generation-old (10GEN) C. neoformans cells are more resistant to phagocytosis and killing by macrophages than younger daughter cells. However, mechanisms that mediate this resistance and intracellular parasitism are poorly understood. Here, we identified important factors for the intracellular survival of 10GEN C. neoformans, such as urease activity, capsule synthesis, and DNA content using flow cytometry and fluorescent microscopy techniques. The real-time visualization of time-lapse imaging was applied to determine the phagosomal acidity, membrane permeability, and vomocytosis (non-lytic exocytosis) rate in J774 macrophages that phagocytosed C. neoformans of different generational ages. Our results showed that old C. neoformans exhibited higher urease activity and enhanced Golgi activity. In addition, old C. neoformans were more likely to be arrested in the G2 phase, resulting in the occasional formation of aberrant trimera-like cells. To finish, the advanced generational age of the yeast cells slightly reduced vomocytosis events within host cells, which might be associated with increased phagolysosome pH and membrane permeability. Altogether, our results suggest that old C. neoformans prevail within acidic phagolysosomes and can manipulate the phagosome pH. These strategies may be used by old C. neoformans to resist phagosomal killing and drive cryptococcosis pathogenesis. The comprehension of these essential host-pathogen interactions could further shed light on mechanisms that bring new insights for novel antifungal therapeutic design.

Unveiling Antibiotic Resistance, Clonal Diversity, and Biofilm Formation in E. coli Isolated from Healthy Swine in Portugal.

Escherichia coli, a commensal microorganism found in the gastrointestinal tract of human and animal hosts, plays a central role in agriculture and public health. Global demand for animal products has promoted increased pig farming, leading to growing concerns about the prevalence of antibiotic-resistant E. coli strains in swine populations. It should be noted that a significant portion of antibiotics deployed in swine management belong to the critically important antibiotics (CIA) class, which should be reserved for human therapeutic applications. This study aimed to characterize the prevalence of antibiotic resistance, genetic diversity, virulence characteristics, and biofilm formation of E. coli strains in healthy pigs from various farms across central Portugal. Our study revealed high levels of antibiotic resistance, with resistance to tetracycline, ampicillin, tobramycin, and trimethoprim-sulfamethoxazole. Multidrug resistance is widespread, with some strains resistant to seven different antibiotics. The ampC gene, responsible for broad-spectrum resistance to cephalosporins and ampicillin, was widespread, as were genes associated with resistance to sulfonamide and beta-lactam antibiotics. The presence of high-risk clones, such as ST10, ST101, and ST48, are a concern due to their increased virulence and multidrug resistance profiles. Regarding biofilm formation, it was observed that biofilm-forming capacity varied significantly across different compartments within pig farming environments. In conclusion, our study highlights the urgent need for surveillance and implementation of antibiotic management measures in the swine sector. These measures are essential to protect public health, ensure animal welfare, and support the swine industry in the face of the growing global demand for animal products.

Homocysteine as a predictor of apnea-hypopnea index in obstructive sleep apnea: a longitudinal epidemiological study (EPISONO).

BACKGROUND: Obstructive sleep apnea (OSA) affects nearly 1 billion people globally, and has established links with cardiovascular and neurocognitive complications. Although it has some limitations, the apnea-hypopnea index (AHI) is commonly used to gauge OSA severity and therapeutic response. Homocysteine (Hcy) metabolism, when impaired, can elicit cellular senescence mechanisms that may be shared with OSA. Hence, our objective was to explore the role of Hcy concentrations both as a predictor of AHI values and as a potential risk factor for OSA. METHODS: Involving 1042 volunteers aged 20 to 80 years, the initial study (2007) included polysomnographic evaluations, questionnaires on sleep and general health, as well as biochemical analyses. After an 8-year interval, 715 participants from the initial study were invited for a follow-up assessment in 2015. RESULTS: Our findings showed that Hcy was a predictor for an increased AHI, and AHI increased over time. Individuals with plasma Hcy concentrations ≥ 15 µmol/L experienced an average AHI increase of 7.43 events/hour ([beta coefficient] ß = 7.43; 95%CI 2.73 to 12.13) over time, compared to those with plasma concentrations < 10 µmol/L. A similar trend was apparent in those with plasma Hcy concentrations between 10 ≥ and < 15 µmol/L, who had an AHI increase with an average beta coefficient of 3.20 events/hour (95%CI 1.01 to 5.39) compared to those with plasma Hcy concentrations < 10 µmol/L. CONCLUSIONS: In summary, our study suggests that increased plasma Hcy concentrations could be considered a risk factor for the development of OSA. These findings highlight that elevated plasma Hcy concentrations can predict the severity of OSA, underscoring their correlation with the AHI.

Unraveling the dual role of ADAM10: Bridging the gap between cancer and Alzheimer's disease.

An inverse association between Alzheimer's disease (AD) and cancer has been proposed. Patients with a cancer history have a decreased risk of developing AD, and AD patients have a reduced cancer incidence, which is not seen in vascular dementia patients. Given this association, common molecular and biological mechanisms that could explain this inverse relationship have been proposed before, such as Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), Wingless and Int-1 (Wnt), and transformation-related protein 53 (p53)-mediated pathways, along with inflammation and oxidative stress-related proteins. A Disintegrin And Metalloprotease 10 (ADAM10) is a protease responsible for the cleavage of key AD- and cancer-related substrates, and it has inverse roles in those diseases: neuroprotective and disease-promoting, respectively. Thus, herein, we review the relevant literature linking AD and cancer and propose how ADAM10 activity might modulate the inverse association between the diseases. Understanding how this protease mediates those two conditions might raise some considerations in the ADAM10 pharmacological modulation for treating AD and cancer.

Assessment of atherosclerosis and endothelial dysfunction risk factors in patients with primary glomerulonephritis / Avaliação dos fatores de risco de aterosclerose e disfunção endotelial em pacientes com glomerulopatias primárias

Abstract Introduction: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. Hypothesis: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. Objective: To evaluate the main markers of atherosclerosis in patients with PG. Method: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. Results: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. Discussion and conclusion: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.

Resumo Introdução: Glomerulopatias são a terceira causa de doença renal crônica (DRC) com necessidade de diálise no Brasil. Distúrbio mineral e ósseo (DMO) é uma das complicações da DRC e está presente já nos estágios iniciais. A avaliação da espessura médio-intimal de carótidas (EMIC) e da vasodilatação fluxo-mediada (VFM) são maneiras não invasivas de avaliação do risco cardiovascular. Hipótese: Pacientes com glomerulopatias primárias (GP) apresentam alta prevalência de aterosclerose e disfunção endotelial, não explicada totalmente pelos fatores de risco tradicionais, mas provavelmente influenciada pela instalação precoce do DMO. Objetivo: Avaliar os principais marcadores de aterosclerose em pacientes com GP. Método: Estudo clínico, observacional, transversal e controlado. Foram incluídos portadores de GP e excluídos menores de 18 anos, gestantes, menos de três meses de seguimento e os com glomerulopatia secundária. Também foram excluídos aqueles que, no momento da coleta, apresentavam proteinúria maior que 6 gramas/24 horas e uso de prednisona em doses superiores a 0,2 mg/kg/dia. Resultados: 95 pacientes foram incluídos, 88 colheram os exames, 1 foi excluído e 23 não realizaram a ultrassonografia. Os pacientes com GP apresentaram maior EMIC média em relação ao controle (0,66 versus 0,60), p = 0,003. Após análise multivariada, mantiveram relevância estatística a idade e os valores de pressão arterial sistólica (PAS), VFM e TFG (p = 0,02) e VFM e ácido úrico sérico (p = 0,048). Discussão e conclusão: Pacientes com GP apresentaram maior risco cardiovascular, entretanto esse risco não foi explicitado pelo DMO precoce. Estudos clínicos randomizados e multicêntricos são necessários para melhor determinação dessa hipótese.

Characteristics of house calls in Brazil: analysis of PMAQ-AB external evaluation cycles.

OBJECTIVE: To analyze characteristics of the home visit (HV) in Brazil, 2012 and 2017. METHODS: Ecological study, with panel data whose units of analysis were the Primary Health Care teams in Brazil, participants of the 1st and 3rd cycles of the Program to Improve Access and Quality of Primary Care of the Unified Health System. Descriptive, inferential and spatial analyzes (alpha=5%) were performed. RESULTS: There was an increase in the proportion of teams that carried out home visits at a frequency defined based on risk and vulnerability analysis and actively searched for people with respiratory symptoms and women with delayed and altered cytopathological examination. In the heat maps, the Northeast, Southeast and South regions had a higher concentration of teams that carried out the HV and carried out an active search. CONCLUSION: The maintenance and qualification of HVs must be a priority in Brazil, since there are few countries in the world with such capillarity of health services, reaching the homes of millions of people.

Calorie restriction protects against acute systemic LPS-induced inflammation.

Caloric restriction (CR) has been proposed as a nutritional strategy to combat chronic diseases, including neurodegenerative diseases, as well as to delay aging. However, despite the benefits of CR, questions remain about its underlying mechanisms and cellular and molecular targets.Objective: As inflammatory processes are the basis or accompany chronic diseases and aging, we investigated the protective role of CR in the event of an acute inflammatory stimulus.Methods: Peripheral inflammatory and metabolic parameters were evaluated in Wistar rats following CR and/or acute lipopolysaccharide (LPS) administration, as well as glial changes (microglia and astrocytes), in two regions of the brain (hippocampus and hypothalamus) involved in the inflammatory response. We used a protocol of 30% CR, for 4 or 8 weeks. Serum and brain parameters were analyzed by biochemical or immunological assays.Results: Benefits of CR were observed during the inflammatory challenge, where the partial reduction of serum interleukin-6, mediated by CR, attenuated the systemic response. In the central nervous system (CNS), specifically in the hippocampus, CR attenuated the response to the LPS, as evaluated by tumor necrosis factor alpha (TNFα) levels. Furthermore, in the hippocampus, CR increased the glutathione (GSH) levels, resulting in a better antioxidant response.Discussion: This study contributes to the understanding of the effects of CR, particularly in the CNS, and expands knowledge about glial cells, emphasizing their importance in neuroprotection strategies.

Study protocol of a randomized controlled trial to assess the efficacy of the "PrEPare for Work" intervention to enhance PrEP uptake and optimize adherence for HIV prevention among male sex workers in the U.S.

BACKGROUND: Male sex workers (MSWs), specifically cisgender men who exchange sex for money, goods, drugs, or other items of value with other cisgender men, are at high risk for HIV infection. Compared to men not engaged in sex work, MSWs are more likely to engage in frequent condomless sex with paying and non-paying sexual partners. While MSWs are often included as a subgroup of gay and bisexual men, data show that a large proportion identify as heterosexual; additionally, most MSWs do not identify as "sex workers." This places MSWs in a unique position where they may not engage with traditional HIV prevention programs, and when they do, they may not feel comfortable, leading to poor retention. Thus, HIV prevention interventions that address MSWs' unique life circumstances and provide support in exploring their sexual health options are needed. METHODS: In this protocol paper, we describe the design and procedures for a National Institute of Health-funded, randomized controlled trial testing the efficacy of "PrEPare for Work,"- a theory-based, manualized PrEP uptake and adherence intervention for MSW - using a 2-stage randomization design. Stage 1: MSWs are equally randomized to receive either the "PrEPare for Work Stage 1 intervention" (strength-based case management and facilitated PrEP linkage) or Standard of Care (SOC) to evaluate successful PrEP uptake (prescription filled) within two months post-randomization. Stage 2: Those who initiate PrEP are then equally re-randomized to receive either the "PrEPare for Work Stage 2 intervention" (1-on-1 skills training, problem-solving, and motivational interviewing adherence counseling and personalized, daily text message reminders) or SOC to assess adherence (Tenofovir concentrations in hair) over 12 months of follow up. Planned analyses will examine intervention efficacy, specific conceptual mediators, and hypothesized moderators. DISCUSSION: Based on our extensive preliminary research, multi-component, theory-informed interventions targeting this subpopulation of MSWs' unique life circumstances are urgently needed. In this study, we are evaluating whether "PrEPare for Work" can improve PrEP uptake and adherence among MSWs. If this intervention is efficacious, it would be readily disseminated to diverse community organizations that serve MSWs and possibly other community or clinic-based settings. TRIAL REGISTRATION: ClinicalTrials.gov number NCT05736614, registered February 8, 2023.

Reduction of Urinary Tract Infection in Pediatric Surgical Patients Using NSQIP-P and Quality Improvement Methodology.

BACKGROUND: Hospital-acquired urinary tract infections (UTIs) have a detrimental effect on patients, families, and hospital resources. The Sydney Children's Hospital Network (SCHN) participates in the NSQIP-Pediatric (NSQIP-P) to monitor postoperative complications. NSQIP-P data revealed that the median UTI rate at SCHN was 1.75% in 2019, 3.5 times higher than the NSQIP-P target rate of 0.5%. Over three quarters of the NSQIP-P identified patients with UTI also had a urinary catheterization performed intraoperatively. A quality improvement project was conducted between mid-2018 and 2021 to minimize catheter-associated UTIs (CAUTIs) at SCHN. STUDY DESIGN: NSQIP-P samples include pediatric (younger than 18 years) surgical patients from an 8-day cycle operative log. NSQIP-P data are statistically analyzed by the American College of Surgeons and provide biannual internationally benchmarked reports. The project used clinical redesign methodology with a 6-phase process for quality improvement projects. RESULTS: The objectives of the project were to reduce urinary catheter duration of use, educate parents or carers, and improve catheter care and insertion technique by health staff. The duration of a urinary catheter in situ reduced from a median of 4.5 to 3 days from 2017 to 2021. The median NSQIP-P UTI rate at SCHN was reduced by 47.4% from 1.75% in 2019 to 0.9% in 2022. CONCLUSIONS: A multifactorial approach in quality improvement has been shown to be an effective strategy to reduce UTI rates at SCHN, and patient outcomes were improved within a 3-year timeframe. Although this project has reduced UTI rates at SCHN, there remain opportunities for further improvement.