Simultaneous photoactivation of a fluoroquinolone antibiotic and nitric oxide with fluorescence reporting.

The achievement of smart pharmaceuticals whose bioactivity can be spatiotemporally controlled by light stimuli is known as photopharmacology, an emerging area aimed at improving the therapeutic outcome and minimizing side effects. This is especially attractive for antibiotics, for which the inevitable development of multidrug resistance and the dwindling of new clinically approved drugs represent the main drawbacks. Here, we show that nitrosation of the fluoroquinolone norfloxacin (NF), a broad-spectrum antibiotic, leads to the nitrosated bioconjugate NF-NO, which is inactive at the typical minimum inhibitory concentration of NF. Irradiation of NF-NO with visible blue light triggers the simultaneous release of NF and nitric oxide (NO). The photouncaging process is accompanied by the revival of the typical fluorescence emission of NF, quenched in NF-NO, which acts as an optical reporter. This permits the real-time monitoring of the photouncaging process, even within bacteria cells where antibacterial activity is switched on exclusively upon light irradiation. The mechanism of photorelease seems to occur through a two-step hopping electron transfer mediated by the lowest triplet state of NF-NO and the phosphate buffer ions or aminoacids such as tyrosine. Considering the well-known role of NO as an "unconventional" antibacterial, the NF-NO conjugate may represent a potential bimodal antibacterial weapon activatable on demand with high spatio-temporal control.

Stepwise Nitric Oxide Release and Antibacterial Activity of a Nitric Oxide Photodonor Hosted within Cyclodextrin Branched Polymer Nanocarriers.

A hydrophobic nitric oxide (NO) photodonor integrating both nitroso and nitro functionalities within its chromophoric skeleton has been synthesized. Excitation of this compound with blue light triggers the release of two NO molecules from the nitroso and the nitro functionalities via a stepwise mechanism. Encapsulation of the NO photodonor within biocompatible neutral, cationic, and anionic ß-cyclodextrin branched polymers as suitable carriers leads to supramolecular nanoassemblies, which exhibit the same nature of the photochemical processes but NO photorelease performances enhanced by about 1 order of magnitude when compared with the free guest. Antibacterial tests carried out with methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii demonstrate an effective antibacterial activity exclusively under light activation and point out a differentiated role of the polymeric nanocarriers in determining the outcome of the antibacterial photodynamic action.

Molecular effects of photodynamic therapy with curcumin on Leishmania major promastigotes.

Leishmaniasis is a neglected disease mainly affecting low-income populations. Conventional treatment involves several side effects, is expensive, and, in addition, protozoa can develop resistance. Photodynamic therapy (PDT) is a promising alternative in treating the disease. PDT involves applying light at a specific wavelength to activate a photosensitive compound (photosensitizer, PS), to produce reactive oxygen species (ROS). Curcumin and its photochemical characteristics make it a good candidate for photodynamic therapy. Studies evaluating gene expression can help to understand the molecular events involved in the cell death caused by PDT. In the present study, RNA was extracted from promastigotes from the control and treated groups after applying PDT. RT-qPCR was performed to verify the expression of the putative ATPase beta subunit (ATPS), ATP synthase subunit A (F0F1), argininosuccinate synthase 1 (ASS), ATP-binding cassette subfamily G member 2 (ABCG2), glycoprotein 63 (GP63), superoxide dismutase (FeSODA), and glucose-6-phosphate dehydrogenase (G6PDH) genes (QR). The results suggest that PDT altered the expression of genes that participate in oxidative stress and cell death pathways, such as ATPS, FeSODA, and G6PD. The ATP-F0F1, ASS, and GP63 genes did not have their expression altered. However, it is essential to highlight that other genes may be involved in the molecular mechanisms of oxidative stress and, consequently, in the death of parasites.

Effects of antimicrobial photodynamic therapy with photodithazine® on methicillin-resistant Staphylococcus aureus (MRSA): Studies in biofilms and experimental model with Galleria mellonella.

Staphylococcus aureus infections are a severe health problem due to the high mortality rate. Conventional treatment of these infections is via the administration of antibiotics. However, its indiscriminate use can select resistant microorganisms. Thus, it is necessary to develop alternatives for antibiotic therapy. Antimicrobial Photodynamic Therapy (aPDT), a therapeutic method that associates a photosensitizer (PS), a light source with adequate wavelength to the PS, interacts with molecular oxygen generating reactive oxygen species responsible for cell inactivation, is a viable alternative. This work aimed to analyze, in vitro and in vivo, the action of aPDT with PS Photodithazine® (PDZ) on the methicillin-resistant S. aureus (MRSA) strain. In the in vitro method, the S. aureus biofilm was incubated with PDZ at 50 and 75 µg.mL-1 for 15 min, adopting the light dose of 25, 50, and 100 J/cm2. In addition, PS interaction, formation of reactive oxygen species (ROS), bacterial metabolism, adhesion, bacterial viability, and biofilm structure were evaluated by scanning electron microscopy. Subsequently, the strain was inoculated into models of Galleria mellonella, and the survival curve, health scale, blood cell analysis, and CFU/mL of S. aureus in the hemolymph were analyzed after aPDT. In the in vitro results, bacterial reduction was observed in the different PDZ concentrations, highlighting the parameters of 75 µg.mL-1 of PDZ and 100 J/cm2. As for in vivo results, aPDT increased survival and stimulated the immune system of G. mellonella infected by S. aureus. aPDT proved effective in both models, demonstrating its potential as an alternative therapy in treating MRSA bacterial infections.

Photodynamic therapy of cationic and anionic BSA-curcumin nanoparticles on amastigotes of Leishmania braziliensis and Leishmania major and Leishmania amazonensis.

Cutaneous leishmaniasis is a neglected disease prevalent in tropical countries, and conventional treatment can cause several serious side effects. Photodynamic therapy (PDT) can be considered a promising treatment alternative, as it is non-invasive therapy that has no side effects and uses accessible and low-cost substances, such as curcumin. This study evaluated the PDT response with cationic and anionic BSA nanoparticles encapsulated with curcumin in macrophages infected with L. braziliensis, L. major, and L. amazonensis. The nanoparticle system was characterized using a steady-state technique, scanning electron microscopy (SEM) study, and its biological activity was evaluated using macrophage cell lines infected with different Leishmania species. All spectroscopy measurements demonstrated that BSA curcumin (BSACur) has good photophysical properties, and confocal microscopy shows that macrophages and protozoa internalized the nanoparticles. The viability test demonstrated that at low concentrations, such as 0.1, 0.7, and 1.0 µmol. L-1, there was a decrease in cell viability after PDT application. Furthermore, a decrease in the number of parasites recovered was observed in the PDT groups. The results allowed us to conclude that curcumin loaded into BSA nanoparticles may have potential application in drug delivery systems for PDT protocols, demonstrating reduced cell viability at lower concentrations than free curcumin.

Effects of 1,3-propanediol associated, or not, with butylene glycol and/or glycerol on skin hydration and skin barrier function.

OBJECTIVE: This study aimed to assess the effect of 1,3-propanediol at different concentrations (5%, 10%, or 15%), either applied alone or in combination with butylene glycol (BG) (5%) and/or glycerol (5%), on skin hydration and skin barrier function. The measurements were conducted using capacitance to determine skin hydration and trans epidermal water loss (TEWL) rates to evaluate skin barrier function. METHODS: A total of 30 healthy female subjects participated in the study. Capacitance and TEWL measurements were conducted at multiple time points, including before application and at 15 min, 2 and 8 h after the humectants were applied to the forearms of the subjects. All the subjects provided written informed consent. RESULTS: The 1,3-propanediol in all concentrations and in all combinations (with BG and/or glycerol) increased skin hydration and improved skin barrier function 15 min, 2 and 8 h after application. Glycerol increased the hydration performance of 1,3-propanediol. The application of 1,3-propanediol at a concentration of 15%, either alone or in combination with other humectants, reduced the TEWL to a greater extent than lower concentrations of 1,3-propanediol. Furthermore, the addition of glycerol to 1,3-propanediol 15% improved the skin barrier and reduced TEWL when compared with 1,3-propanediol alone and with the combination of 1,3-propanediol + BG. CONCLUSION: The humectants significantly improved skin hydration and reduced TEWL throughout the 8-h time course. The increase in 1,3-propanediol concentration, as well as its combination with glycerol, provided a greater benefit to the skin, improving both hydration and the skin barrier function.

OBJECTIF: Cette étude visait à évaluer l'effet sur l'hydratation de la peau et la fonction de barrière cutanée du 1,3-propanediol à différentes concentrations (5 %, 10 % ou 15 %), appliqué seul ou en association avec du butylène glycol (5 %) et/ou du glycérol (5 %). Les mesures ont été effectuées à l'aide de la capacitance pour déterminer l'hydratation de la peau et les taux de perte d'eau transépidermique (Trans Epidermal Water Loss, TEWL) pour évaluer la fonction de barrière cutanée. MÉTHODES: Au total, 30 sujets de sexe féminin en bonne santé ont participé à l'étude. Les mesures de la capacitance et de la TEWL ont été effectuées à plusieurs moments, y compris avant l'application, 15 minutes, 2 heures et 8 heures après l'application des produits humectant sur les avant-bras des sujets. Tous les sujets ont fourni un consentement éclairé écrit. RÉSULTATS: Le 1,3-propanediol, à toutes les concentrations et dans toutes les associations (avec le butylène glycol et/ou le glycérol), a augmenté l'hydratation de la peau et amélioré la fonction de barrière cutanée à 15 minutes, 2 heures et 8 heures après l'application. Le glycérol a augmenté les performances d'hydratation du 1,3-propanediol. L'application de 1,3-propanediol à une concentration de 15 %, seul ou en association avec d'autres produits humectant, a réduit la TEWL dans une plus grande mesure que des concentrations inférieures de 1,3-propanediol. En outre, l'ajout de glycérol au 1,3-propanediol 15 % a amélioré la barrière cutanée et réduit la TEWL par rapport au 1,3-propanediol seul et à l'association 1,3-propanediol + butylène glycol. CONCLUSION: Les produits humectant ont significativement amélioré l'hydratation de la peau et réduit la TEWL tout au long des 8 heures. L'augmentation de la concentration de 1,3-propanediol, ainsi que son association avec le glycérol, ont apporté un plus grand bénéfice à la peau, améliorant à la fois l'hydratation et la fonction de barrière cutanée.

Factors Related to Recurrent Falls Among Older Adults Attending Primary Health Care: A Biopsychosocial Perspective.

The objective of this study was to investigate factors related to recurrent falls among older adults attending primary health care, considering the biopsychosocial perspective. A representative sample of 201 older adults were interviewed in three Primary Health Care units randomly selected in a city in southeastern Brazil. Outcome included self-report of two or more falls in the past 12 months. Exposures included personal and environmental aspects, according to domains of International Classification of Functioning of the World Health Organization (ICF-WHO). Recurrent falls were reported by 24.4% of the participants. Associations with depressive symptoms (p = .003), having osteoporosis (p = .031), chronic musculoskeletal pain (p = .020), frailty (p = .013), sleep satisfaction (p < .001), and functional status (p < .001) were found. In logistic regression models, cognitive status, musculoskeletal pain, and functional status were predictors of recurrent falls; however, only sleep satisfaction remained significant in the final model. Strategies aimed at preventing recurrent falls in primary health care should consider assessments and interventions targeting sleep aspects among older adults.

Adverse effects of topical photodynamic therapy in rosacea - Case report.

Rosacea is a chronic and inflammatory skin condition, with relapses being a common characteristic. Its treatments are based on cosmetics, drugs, and the application of procedures based on high-powered light. Photodynamic Cosmetic Therapy (PCT) combines light, a photosensitizer (PS), and molecular oxygen present in tissues, generating photochemical reactions capable of causing tissue and vascular destruction, stimulating tissue repair. We report a case with an adverse effect caused by applying PCT, using 2 % 5-aminolevulinic acid (ALA 2 %), and irradiated with amber LED light associated with infrared radiation for the control of rosacea. A patient with subtype II rosacea underwent PCT treatment of 3 sessions at 21-day intervals, being evaluated using photographic images and Wood's lamp. In the first session of the therapy, an exacerbated inflammatory process was observed. Such an adverse event is estimated to be as a result of the patient using ointment containing corticosteroids for a short period. With the use of medications, it was possible to recover the appearance of the skin thoroughly, and after 21 days, the treatment sessions were performed again. Despite the complication that affected the patient in this study, positive effects were found after the pharmacological therapeutic measures were adopted.

Factors predicting hospital admission and death in older adults with cognitive impairment: a longitudinal study / Factores predictivos de hospitalización y muerte en ancianos con deterioro cognitivo: un estudio longitudinal / Fatores preditores de hospitalização e óbito em idosos com comprometimento cognitivo: um estudo longitudinal

ABSTRACT Objective: to identify sociodemographic factors, clinical conditions and sarcopenia parameters that predict hospital admission and death in older adults with cognitive impairment. Method: this is a longitudinal observational study carried out with 170 older adults with cognitive impairment assessed between 2019 and 2021. Predictor variables were sociodemographic characteristics, clinical conditions and sarcopenia parameters. Sarcopenia was operationalized through handgrip muscle strength (dynamometry), muscle mass (calf circumference) and the Timed Up and Go test. Occurrence of hospital admission and death within one year after assessment of older adults were the predicted variables. Analyzes were carried out using descriptive statistics, independent Student' t-test, Mann-Whitney U test, chi-square test and univariate logistic regression. Results: most participants were female (±77.57 years old), with low education, sedentary, 15.9% with sarcopenia and 13% with a history of hospital admission. It was identified that education level had an effect on occurrence of hospital admission (U=1,423.5, p=0.027) and death (U=647.0, p=0.025) within one-year follow-up. Furthermore, there is an association between history of hospital admission in the last 6 months and occurrence of hospital admission [χ2(1)=4.729; p=0.030] and death [χ2(1)=3.919; p=0.048] within one year follow-up. It was identified that history of hospital admission in the last 6 months was associated with occurrence of hospital admission within one-year follow-up (OR=2.963; 95%CI 1.076-8.165, p=0.036). Conclusion: history of hospital admission in the last six months is associated with occurrence of hospital admission over a year in older adults with cognitive impairment.

RESUMEN Objetivo: identificar factores sociodemográficos, condiciones clínicas y parámetros de sarcopenia que predicen la hospitalización y la muerte en personas mayores con deterioro cognitivo. Método: estudio observacional longitudinal realizado con 170 personas mayores con deterioro cognitivo evaluados entre 2019 y 2021. Las variables predictoras fueron las características sociodemográficas, las condiciones clínicas y los parámetros de sarcopenia. La sarcopenia se puso en práctica mediante la fuerza de los músculos de prensión manual (dinamometría), la masa muscular (circunferencia de la pantorrilla) y la prueba Timed Up and Go. La ocurrencia de hospitalización y muerte dentro del año posterior a la evaluación del anciano configuró las variables predichas. Los análisis se realizaron mediante estadística descriptiva las pruebas t de Student independiente, U de Mann-Whitney, chi-cuadrado y regresión logística univariada. Resultados: la mayoría de los participantes fueron del sexo femenino (±77,57 años), con bajo nivel educativo, sedentarios, el 15,9% con sarcopenia y el 13% con antecedentes de hospitalización. Se identificó que el nivel de escolaridad tuvo efecto en la ocurrencia de hospitalización (U=1.423,5, p=0,027) y muerte (U=647,0, p=0,025) al año de seguimiento. Además, existe asociación entre el antecedente de hospitalización en los últimos 6 meses y la ocurrencia de hospitalización [χ2(1)=4,729; p=0,030] y muerte [χ2(1)=3,919; p=0,048] al año de seguimiento. Se identificó que el antecedente de hospitalización en los últimos 6 meses se asoció con la ocurrencia de hospitalización en un año de seguimiento (OR=2,963; IC95% 1,076-8,165, p=0,036). Conclusión: un antecedente de hospitalización en los últimos seis meses se asocia con la ocurrencia de hospitalización mayor a un año en personas mayores con deterioro cognitivo.

RESUMO Objetivo: identificar fatores sociodemográficos, condições clínicas e parâmetros de sarcopenia preditores de hospitalização e óbito em idosos com comprometimento cognitivo. Método: estudo observacional longitudinal realizado com 170 idosos com comprometimento cognitivo avaliados entre 2019 e 2021. As variáveis preditoras foram características sociodemográficas, condições clínicas e parâmetros de sarcopenia. A sarcopenia foi operacionalizada por meio da força muscular de preensão palmar (dinamometria), da massa muscular (circunferência da panturrilha) e do teste Timed Up and Go. A ocorrência de hospitalização e óbito até um ano após a avaliação do idoso configuraram as variáveis preditas. Procedeu-se análises por estatística descritiva, testes t-student independente, U Mann Whitney, Qui-Quadrado e de regressão logística univariada. Resultados: a maioria dos participantes era do sexo feminino (±77,57 anos), de baixa escolaridade, sedentários, 15,9% com sarcopenia e 13% com histórico de internação. Foi identificado que o nível de escolaridade teve efeito sobre a ocorrência de hospitalização (U=1423,5, p=0,027) e de óbito (U=647,0, p=0,025) no seguimento de um ano. Além disso, há associação do histórico de internação nos últimos 6 meses com a ocorrência de hospitalização [χ2(1)=4,729; p=0,030] e de óbito [χ2(1)=3,919; p=0,048] no seguimento de um ano. Identificou-se que o histórico de internação nos últimos 6 meses associou-se com a ocorrência de hospitalização em um ano de seguimento (OR=2,963; IC95% 1,076-8,165, p=0,036). Conclusão: o histórico de internação nos últimos seis meses está associado à ocorrência de hospitalização ao longo de um ano em idosos com comprometimento cognitivo.

Preventing the next fragility fracture: a cross-sectional survey of secondary fragility fracture prevention services worldwide.

BACKGROUND: There has been an increasing awareness of the public health impact of fragility fractures due to osteoporosis and the imperative of addressing this health burden with well-designed secondary fragility fracture prevention services (SFFPS). The objectives of this survey, conducted within the international membership of the Fragility Fracture Network (FFN), were to identify gaps in services and identify the needs for further training and mentorship to improve the quality of SFFPS provided to patients who sustain fragility fractures. METHODS: We conducted an electronic cross-sectional survey of FFN Secondary Fracture Prevention Special Interest Group (SIG) members from April 2021 to June 2021 using SurveyMonkey. The survey questions were developed by four SIG members from New Zealand, Australia, Canada and the Netherlands, who have experience in developing, implementing and evaluating SFFPS. The sampling framework was convenience sampling of all 1162 registered FFN Secondary Fracture Prevention SIG members. Descriptive analyses were performed for all variables and presented as frequencies and percentages. RESULTS: 69 individuals participated in the survey, from 34 different countries over six continents, with a response rate of 6% (69/1162). Almost one-third of respondents (22/69) were from 15 countries within the European continent. Key findings included: (1) 25% of SFFPS only included patients with hip fracture; (2) less than 5% of SFFPS had any mandatory core competencies for training; (3) 38.7% of SFFPS were required to collect key performance indicators; and (4) 9% were collecting patient-reported outcome measures. CONCLUSIONS: This survey identified key areas for improving SFFPS, including: expanding the reach of SFFPS to more patients with fragility fracture, developing international core competencies for health provider training, using key performance indicators to improve SFFPS and including the patient voice in SFFPS development. These findings will be used by the FFN to support SFFPS development internationally.

Hydroxyapatite microspheres used as a drug delivery system for gliosarcoma strain 9l/Lacz treatment by photodynamic therapy protocols.

BACKGROUND: Hydroxyapatite (HAp) presents similarities with the human bone structure and presents properties such as biodegradability, biocompatibility, and osteoconductivity, which favors its use in prostheses implants and enables its use as a vehicle for the delivery of photosensitizers (PS) from systems of release (DDS) for photodynamic therapy applications Methods: In this work was to synthesized hydroxyapatite microspheres (meHAp), encapsulated with chloroaluminium phthalocyanine (ClAlPc), for DDS. meHAp was synthesized using vaterite as a template. The drug was encapsulated by mixing meHAp and a 50.0 mg.mL-1 ClAlPc solution. Photochemical, photophysical, and photobiological studies characterized the system. RESULTS: The images from the SEM analysis showed the spherical form of the particles. All spectroscopic results showed excellent photophysical parameters of the drug studied when served in the meHAp system. The incorporation efficiency was 57.8 %. The trypan blue exclusion test results showed a significant reduction (p < 0.05) in cell viability for the groups treated with PDT at all concentrations above 250 µg.mL-1. In 9 L/lacZ gliosarcoma cells, PDT mediated at concentrations from 250 to 62.5 µg.mL-1 reduced cell viability by more than 98 %. In the cell internalization study, it was possible to observe the internalization of phthalocyanines at 37 °C, with the accumulation of PS in the cytoplasm and inside the nucleus in the two tested concentrations. CONCLUSIONS: From all the results presented throughout the article, the meHAp system shows promise for use as a modified release system (DSD) in photodynamic therapy.

Social support network, functional capacity and mental health in older adults / Rede de suporte social, capacidade funcional e saúde mental em pessoas idosas / Red de apoyo social, capacidad funcional y salud mental en personas mayores

This study aimed to describe the characteristics of the social networks of older adults and to assess associations between social support, functional capacity and mental health. The sample consisted of 134 community-dwelling older adults, assessed in terms of their social network through the Minimum Map of Older Adult Relationships; functional capacity for performance in activities of daily living; depressive symptoms, assessed through the Geriatric Depression Scale and; anxiety, assessed through the Beck Anxiety Inventory. Cluster analyses were performed. The social network was characterized by being informal, functioning as affective support that occurs through visits. Social support perceived as insufficient was more frequent in men, in those who were dependent regarding instrumental activities of daily living, and in those with anxiety and depressive symptoms. Reduced social support networks and lack of support were associated with limitations in functional capacity and worse mental health, sparking debate about the centrality of the family in the provision of support.(AU)

Este estudo objetivou descrever as características da rede social de pessoas idosas e avaliar associações entre apoio social, capacidade funcional e saúde mental. A amostra foi composta por 134 idosos comunitários, avaliados quanto à rede social pelo Mapa Mínimo das Relações do Idoso; capacidade funcional pelo desempenho em atividades de vida diária; sintomas depressivos, avaliados pela Escala de Depressão Geriátrica e; ansiedade, avaliada pelo Inventário de Ansiedade de Beck. Foram realizadas análises de conglomerados. A rede social caracterizou-se por ser informal, funcionando como suporte afetivo que ocorre por meio de visitas. O apoio social percebido como insuficiente foi mais frequente no sexo masculino, entre idosos dependentes em atividades instrumentais de vida diária, com ansiedade e sintomas depressivos. Redes de suporte social reduzidas e com baixo apoio estão associadas com limitações na capacidade funcional e pior saúde mental, colocando em debate a centralidade da família na provisão de suporte.(AU)

Este estudio tuvo como objetivo describir las características de la red social de personas mayores y evaluar las asociaciones entre el apoyo social, la capacidad funcional y la salud mental. La muestra estuvo compuesta por 134 ancianos comunitarios, quienes fueron evaluados en cuanto a su red social mediante el Mapa Mínimo de Relaciones del Anciano; su capacidad funcional en las actividades de la vida diaria; los síntomas depresivos mediante la Escala de Depresión Geriátrica; y la ansiedad a través del Inventario de Ansiedad de Beck. Se realizaron análisis de conglomerados. La red social se caracterizó por ser informal, funcionando como apoyo afectivo que se manifiesta a través de visitas. El apoyo social percibido como insuficiente fue más frecuente en el sexo masculino, entre los ancianos dependientes en actividades instrumentales de la vida diaria, y aquellos con síntomas de ansiedad y depresión. Las redes de apoyo social reducidas y con bajo apoyo se asocian con limitaciones en la capacidad funcional y un peor estado de salud mental, lo que plantea el debate sobre el papel central de la familia en la provisión de apoyo.(AU)

AKT inhibition generates potent polyfunctional clinical grade AUTO1 CAR T-cells, enhancing function and survival.

BACKGROUND: AUTO1 is a fast off-rate CD19-targeting chimeric antigen receptor (CAR), which has been successfully tested in adult lymphoblastic leukemia. Tscm/Tcm-enriched CAR-T populations confer the best expansion and persistence, but Tscm/Tcm numbers are poor in heavily pretreated adult patients. To improve this, we evaluate the use of AKT inhibitor (VIII) with the aim of uncoupling T-cell expansion from differentiation, to enrich Tscm/Tcm subsets. METHODS: VIII was incorporated into the AUTO1 manufacturing process based on the semiautomated the CliniMACS Prodigy platform at both small and cGMP scale. RESULTS: AUTO1 manufactured with VIII showed Tscm/Tcm enrichment, improved expansion and cytotoxicity in vitro and superior antitumor activity in vivo. Further, VIII induced AUTO1 Th1/Th17 skewing, increased polyfunctionality, and conferred a unique metabolic profile and a novel signature for autophagy to support enhanced expansion and cytotoxicity. We show that VIII-cultured AUTO1 products from B-ALL patients on the ALLCAR19 study possess superior phenotype, metabolism, and function than parallel control products and that VIII-based manufacture is scalable to cGMP. CONCLUSION: Ultimately, AUTO1 generated with VIII may begin to overcome the product specific factors contributing to CD19+relapse.

Vaterite microparticle-loaded methylene blue for photodynamic activity in macrophages infected with Leishmania braziliensis.

Calcium carbonate (CaCO3) exhibits a variety of crystalline phases, including the anhydrous crystalline polymorphs calcite, aragonite, and vaterite. Developing porous calcium carbonate microparticles in the vaterite phase for the encapsulation of methylene blue (MB) as a photosensitizer (PS) for use in photodynamic therapy (PDT) was the goal of this investigation. Using an adsorption approach, the PS was integrated into the CaCO3 microparticles. The vaterite microparticles were characterized by scanning electron microscopy (SEM) and steady-state techniques. The trypan blue exclusion method was used to measure the biological activity of macrophages infected with Leishmania braziliensis in vitro. The vaterite microparticles produced are highly porous, non-aggregated, and uniform in size. After encapsulation, the MB-loaded microparticles kept their photophysical characteristics. The carriers that were captured allowed for dye localization inside the cells. The results obtained in this study indicated that the MB-loaded vaterite microparticles show promising photodynamic activity in macrophages infected with Leishmania braziliensis.

Fourier Transform Infrared Spectroscopy (FT-IR) of Pseudomonas aeruginosa post photodynamic therapy with Curcumin in vitro.

Alternative therapies against pathogens are under intense investigation because of their increasing resistance to antibiotics. Photodynamic therapy (PDT) is one such alternative that has shown promising results. However, for the widespread use of PDT, it is essential to decipher underlying mechanisms, so as to improve PDT's therapeutic applications. Because of this, we have studied biochemical changes in pathogen Pseudomonas aeruginosa, a medically important bacteria that has developed antibiotic resistance, after PDT with curcumin photosensitizer. Results show a drastic decrease in α-helix protein and increased disordered and ß-sheet secondary structure proteins in P. Aeruginosa post-PDT compared to control. Interestingly, these biochemical changes differ from PDT of pathogens Leishmania braziliensis and Leishmania major with photosensitizer methylene blue. This observation underlines the need for extensive studies on PDT of different pathogens to understand mechanisms of action and develop better PDT strategies.

Reduced circulating folate among older adults caused by continuous work: nested cross-sectional study conducted in a country with folic acid fortification program.

Population aging is 1 of the biggest challenges facing public health today, and cognitive dysfunction is an important concern. Cognitive impairment may be associated with high folate concentrations and low vitamin B12 concentrations; the latter is a common problem among elderly people. Therefore, we hypothesized there was a high circulating folate concentration among older people living in a country with a mandatory folic acid fortification program. We conducted a cross-sectional study to investigate nutritional status of folate and vitamin B12 among aged people. Three dietary recalls, serum folate (sfolate), erythrocyte (red blood cell) folate (RBC folate), and serum vitamin B12 and homocysteine were collected. Linear regression models were used to investigate factors associated with circulating vitamins. We interviewed 169 participants. Half reported inadequate consumption of folate. However, RBC folate deficiency was observed in 27%, 13% in the serum, and a 10% excess of sfolate. One-quarter reported inadequate consumption of B12, but only 5% had deficiency. Factors negatively associated with circulating folate were continuous work and smoking, and positively associated with polyunsaturated fatty acid. Factor negatively associated with the circulating B12 were use of a dental prosthesis and intake of saturated fatty acid. Permanent investigation of excess of sfolate and B12 deficiency, especially among older adults living in countries exposed to a mandatory folic acid fortification program, is important because of the possible relation to the cognitive function.

Nurse's performance in the hospital discharge process of children with chronic disease.

OBJECTIVE: To analyze the nurse's performance in the hospital discharge process of children with chronic disease. METHOD: Qualitative research conducted from May to August/2019 with ten nurses working in a pediatric unit of a public hospital. The data, collected through semi-structured interviews, were submitted to inductive thematic analysis. RESULTS: In the preparation for hospital discharge, nurses recognize health education as their attribution, valuing family knowledge in the training regarding home care. Nevertheless, their practice is weakened by the little articulation among the multiprofessional team, reduced nursing sizing and disarticulation in the health care network. CONCLUSION: There is a paradox between the report and the practice of the hospital discharge process accomplished by nurses. Although they have theoretical knowledge, their work process is influenced by the disarticulated way in which the multiprofessional team interacts, and the conditions provided by the institution to work in the preparation for hospital discharge of these children.

Predictive Factors for the Risk of Sexual Dysfunction in Climacteric Women: Population-based Study.

BACKGROUND: It is known that sexual problems increase with age but little is known about the predictors of female sexual dysfunction (FSD) in Brazilian climacteric women. AIM: To identify predictive factors for FSD in climacteric women. METHODS: This is a cross-sectional population-based study carried out through a household survey. OUTCOMES: The measures investigated were sociodemographic characteristics, depressive symptoms, level of physical activity, presence of FSD, self-rated health and sleep satisfaction. RESULT: A total of 381 climacteric, sexually active women were included, with a mean age of 55.04 (±7.21) years. The prevalence of FSD was 38.3%. All variables investigated were associated with FSD (P < .05). In the final model, the predictors for FSD were low satisfaction with sleep (OR 4.20; 95% CI 2.32-7.62), advanced age (OR 1.04; 95% CI 1.00-1.08), low education level (OR 0.90; 95% CI 0.85-0.97) and having a partner (OR 0.35; 95% CI 0.16-0.76). CLINICAL IMPLICATION: These aspects deserve attention from the health team to prevent and identify FSD early in life in climacteric women. STRENGTHS & LIMITATIONS: This study support existing data about risk factors for FSD in climacteric women. However, it is not possible to attribute causality to any of the correlates identified, which is a limitation of cross-sectional studies. CONCLUSION: Dissatisfaction with sleep, senility, insufficient income, low education, not having a partner, complaints of depression, and the worse perception of global health are predictive factors for FSD in climacteric women. Romano Marquez Reis SC, Martins Pinto J, Aparecida Porcatti de Walsh I, et al. Predictive Factors for the Risk of Sexual Dysfunction in Climacteric Women: Population-based Study. J Sex Med 2022;19:1546-1552.

Curcuma longa L. Extract and Photodynamic Therapy are Effective against Candida spp. and Do Not Show Toxicity In Vivo.

Radiotherapy induces a higher level of Candida spp. colonization, resulting in oral candidiasis. This study aimed to evaluate the phototransformation potential of the glycolic extract of Curcuma longa (C. longa); the antifungal activity of C. longa, curcumin, and antifungal photodynamic therapy (aPDT) with blue light-emitting diodes "LED" on Candida albicans and Candida tropicalis in vitro; and the toxicity of C. longa and curcumin in Galleria mellonella model. In order to confirm the light absorption capacity of the C. longa extract, its phototransformation potential was evaluated. The antifungal effect of C. longa, curcumin, and aPDT was evaluated over Candida spp. Finally, the toxicity of C. longa and curcumin was evaluated on the Galleria mellonella model. The data were analyzed using the GraphPad Prism 5.0 software considering α = 5%. It was found that C. longa, curcumin, and aPDT using blue LED have an antifungal effect over C. albicans and C. tropicalis. The extract of C. longa 100 mg/mL and curcumin 200 µg/mL do not show toxicity on Galleria mellonella model.

Factors related to the accumulation of healthy behavior among older adults attending primary Health Care.

The adoption and maintenance of healthy behaviors contribute for its accumulation throughout life, which require more than information disclosure and recommendations. Biopsychosocial factors may work as barriers to adherence to healthier behaviors, and yet have been underexplored. The objective was to investigate the factors related to the accumulation of healthy behavior among older adults attending Primary Health Care. Cross-sectional analysis with 201 older adults from baseline of Longitudinal Investigation of Functioning Epidemiology (LIFE) was performed in a Southeastern Brazilian city. The Healthy Behavior Score (HBS), ranging from 0 to 8, was calculated by the sum of the following habits: Physical activity practice, healthy eating, water consumption, night sleep time, not smoking, not drinking alcohol, frequent social relations, and spirituality. A linear multivariate regression was performed to test the influence of biopsychosocial aspects on HBS, with 95% confidence interval. Higher number of healthy behaviors was related to high social support, better cognitive status, less depressive symptoms and lower functional performance. Additionally, age and resilience score were correlated to healthy behaviors, which were higher among women and those with sufficient income. Multivariate analysis revealed depressive symptoms, functional performance and education as independent predictors of HBS. Depressive symptoms, functional performance and education are predictors of accumulation of health behaviors, independently of health status, contextual and sociodemographic aspects. Higher social support partially contributed to the higher number of healthy behaviors, and should be considered in public health policies for healthy longevity.