Regulation of Absorption and Emission in a Protein/Fluorophore Complex.

Human cellular retinol binding protein II (hCRBPII) was used as a protein engineering platform to rationally regulate absorptive and emissive properties of a covalently bound fluorogenic dye. We demonstrate the binding of a thio-dapoxyl analog via formation of a protonated imine between an active site lysine residue and the chromophore's aldehyde. Rational manipulation of the electrostatics of the binding pocket results in a 204 nm shift in absorption and a 131 nm shift in emission. The protein is readily expressed in mammalian systems and binds with exogenously delivered fluorophore as demonstrated by live-cell imaging experiments.

Molecular behavior of silicone adhesive at buried polymer interface studied by molecular dynamics simulation and sum frequency generation vibrational spectroscopy.

Silicones have excellent material properties and are used extensively in many applications, ranging from adhesives and lubricants to electrical insulation. To ensure strong adhesion of silicone adhesives to a wide variety of substrates, silane-based adhesion promotors are typically blended into the silicone adhesive formulation. However, little is known at the molecular level about the true silane adhesion promotion mechanism, which limits the ability to develop even more effective adhesion promoters. To understand the adhesion promotion mechanism of silane molecules at the molecular level, this study has used sum frequency generation vibrational spectroscopy (SFG) to determine the behavior of (3-glycidoxypropyl)trimethoxy silane (γ-GPS) at the buried interface between poly(ethylene terephthalate) (PET) and a bulk silicone adhesive. To complement and extend the SFG results, atomistic molecular dynamics (MD) simulations were applied to investigate molecular behavior and interfacial interaction of γ-GPS at the silicone/PET interface. Free energy computations were used to study the γ-GPS interaction in the sample system and determine the γ-GPS interfacial segregation mechanism. Both experiments and simulations consistently show that γ-GPS molecules prefer to segregate at the interface between PET and PDMS. The methoxy groups on γ-GPS molecules orient toward the PDMS polymer phase. The consistent picture of interfacial structure emerging from both simulation and experiment provides enhanced insight on how γ-GPS behaves in the silicone - PET system and illustrates why γ-GPS could improve the adhesion of silicone adhesive, leading to further understanding of silicone adhesion mechanisms useful in the design of silicone adhesives with improved performance.

Elucidating the Changes in Molecular Structure at the Buried Interface of RTV Silicone Elastomers during Curing.

Silicone elastomers are widely used in many industrial applications, including coatings, adhesives, and sealants. Room-temperature vulcanized (RTV) silicone, a major subcategory of silicone elastomers, undergoes molecular structural transformations during condensation curing, which affect their mechanical, thermal, and chemical properties. The role of reactive hydroxyl (-OH) groups in the curing reaction of RTV silicone is crucial but not well understood, particularly when multiple sources of hydroxyl groups are present in a formulated product. This work aims to elucidate the interfacial molecular structural changes and origins of interfacial reactive hydroxyl groups in RTV silicone during curing, focusing on the methoxy groups at interfaces and their relationship to adhesion. Sum frequency generation (SFG) vibrational spectroscopy is an in situ nondestructive technique used in this study to investigate the interfacial molecular structure of select RTV formulations at the buried interface at different levels of cure. The primary sources of hydroxyl groups required for interfacial reactions in the initial curing stage are found to be those on the substrate surface rather than those from the ingress of ambient moisture. The silylation treatment of silica substrates eliminates interfacial hydroxyl groups, which greatly impact the silicone interfacial behavior and properties (e.g., adhesion). This study establishes the correlation between interfacial molecular structural changes in RTV silicones and their effect on adhesion strength. It also highlights the power of SFG spectroscopy as a unique tool for studying chemical and structural changes at RTV silicone/substrate interface in situ and in real time during curing. This work provides valuable insights into the interfacial chemistry of RTV silicone and its implications for material performance and application development, aiding in the development of improved silicone adhesives.

Microalgae-based domestic wastewater treatment: a review of biological aspects, bioremediation potential, and biomass production with biotechnological high-value.

This review aims to perform an updated bibliographical survey on the cultivation of microalgae in domestic wastewater with a focus on biotechnological aspects. It was verified that the largest number of researches developed was about cultures in microalgae-bacteria consortium and mixed cultures of microalgae, followed by researches referring to the species Chlorella vulgaris and to the family Scenedesmaceae. According to published studies, these microorganisms are efficient in the biological treatment of domestic wastewater, as well as in the production of high value-added biomass, as they are capable of biosorbing the organic and inorganic compounds present in the culture medium, thus generating cells with high levels of lipids, proteins, and carbohydrates. These compounds are of great importance for different industry sectors, such as pharmaceuticals, food, and also for agriculture and aquaculture. In addition, biomolecules produced by microalgae can be extracted for several biotechnological applications; however, most studies focus on the production of biofuels, with biodiesel being the main one. There are also other emerging applications that still require more in-depth research, such as the use of biomass as a biofertilizer and biostimulant in the production of bioplastic. Therefore, it is concluded that the cultivation of microalgae in domestic wastewater is a sustainable way to promote effluent bioremediation and produce valuable biomass for the biobased industry, contributing to the development of technology for the green economy.

Investigation of an outbreak of disease compatible with scurvy in a male penitentiary in the state of Ceará, Brazil, 2019-2020: a case-control study.

MAIN RESULTS: An outbreak of illness compatible with scurvy occurred among male prison inmates; most frequent signs/symptoms were edema and pain in lower limbs, difficulty in walking and hematoma/ecchymosis; the associated factor was age > 40 years. IMPLICATIONS FOR SERVICES: The results can contribute to the identification and description of scurvy outbreaks in other contexts and territories. Epidemiological studies of events like this enhance the practice of field epidemiology in health services. PERSPECTIVES: It is expected that the prevention of hypovitaminosis, such as scurvy, will be based on public policies aimed at the population deprived of liberty; and that the capabilities of health services to detect and respond to cases of the disease will be improved. OBJECTIVE: to identify the occurrence of an outbreak compatible with scurvy and exposure factors associated with typical signs/symptoms of hypovitaminosis that occurred in a male penitentiary in Ceará, Brazil between 2019-2020. METHODS: this was a population-based case-control study; we used clinical records and interviews with compatible cases - based on sign/symptom onset during the study period - and with controls; we carried out multivariate analysis. RESULTS: out of 62 cases, mean age was 40.6 years (SD = 10.8); main signs/symptoms were edema and pain in the lower limbs (100.0%), difficulty in walking (91.9%), hematoma/ecchymosis in the lower limbs (90.3%) and fever (88.7%); we identified being over 40 years old as an associated factor (aOR = 1.10; 95%CI 1.05;1.17; p-value = 0.001); and as protective factors: working (aOR = 0.11; 95%CI 0.03;0.36; p-value < 0.001) and taking part in classes (aOR = 0.21; 95%CI 0.08;0.59; p-value = 0.003) in the prison. CONCLUSION: we considered the penitentiary outbreak to be compatible with scurvy due to characteristic signs/symptoms, associated with the identified factors; we recommended regular provision of a diet rich in vitamin C to all male inmates and clinical follow-up of cases.

Structural Dynamics in the Presence of Water of Graphene Bilayers with Defects.

The dynamics of a bilayer of graphene containing one mono-vacancy in the top layer has been investigated in the framework of DFTB in the absence and in the presence of water. Due to the speed of the code, we can describe details of the behavior, which are not directly accessible experimentally and cannot be treated by DFT or classical molecular dynamics. The presence of water enhances the displacement of carbon atoms in the perpendicular direction to the surface. Our results explain very well a variety of experimental findings. In particular, the stabilization of the Jahn-Teller distortion by hydrogenation of one of the carbon atoms at the edge of a mono-vacancy has been elucidated. This work is the first analysis of the behavior of a graphene vacancy at room temperature in contact with water based on a quantum mechanical molecular dynamics method, where both graphene and solvent are treated at the same level.

Myositis Ossificans of the Breast Mimicking Breast Cancer: A Case Report.

Myositis ossificans (MO) is an uncommon tumor characterized by a rapidly growing mass following a history of local trauma. Few cases of MO affecting the breast have been reported, and some were misdiagnosed as primary osteosarcoma of the breast or metaplastic breast carcinoma. The following case report presents a patient with a growing breast lump whose core biopsy result was suspicious for breast cancer. MO was diagnosed after analysis of the mastectomy specimen. This case highlights the importance of MO as a differential diagnosis of a growing soft-tissue mass after trauma to avoid unnecessary overtreatment. Keywords: Myositis Ossificans, Osteosarcoma, Breast Cancer, Mastectomy, Heterotopic Ossification © RSNA, 2023.

Combined Tumor-Based BRCA1/2 and TP53 Mutation Testing in Ovarian Cancer.

Somatic/germline BRCA1/2 mutations (m)/(likely) pathogenic variants (PV) (s/gBRCAm) remain the best predictive biomarker for PARP inhibitor efficacy. As >95% of high-grade serous ovarian cancers (HGSOC) have a somatic TP53m, combined tumor-based BRCA1/2 (tBRCA) and TP53 mutation testing (tBRCA/TP53m) may improve the quality of results in somatic BRCAm identification and interpretation of the 'second hit' event, i.e., loss of heterozygosity (LOH). A total of 237 patients with HGSOC underwent tBRCA/TP53m testing. The ratio of allelic fractions (AFs) for tBRCA/TP53m was calculated to estimate the proportion of cells carrying BRCAm and to infer LOH. Among the 142/237 gBRCA results, 16.2% demonstrated a pathogenic/deleterious variant (DEL) gBRCA1/2m. Among the 195 contributive tumor samples, 43 DEL of tBRCAm (22.1%) were identified (23 gBRCAm and 20 sBRCAm) with LOH identified in 37/41 conclusive samples. The median AF of TP53m was 0.52 (0.01-0.93), confirming huge variability in tumor cellularity. Initially, three samples were considered as wild type with <10% cellularity. However, additional testing detected a very low AF (<0.05) in both BRCA1/2m and TP53m, thus reidentifying them as sBRCA1/2m. Combined tBRCA/TP53m testing is rapid, sensitive, and identifies somatic and germline BRCA1/2m. AF TP53m is essential for interpreting sBRCA1/2m in low-cellularity samples and provides indirect evidence for LOH as the 'second hit' of BRCA1/2-related tumorigenesis.

Pseudobombax parvifolium Hydroalcoholic Bark Extract: Chemical Characterisation and Cytotoxic, Mutagenic, and Preclinical Aspects Associated with a Protective Effect on Oxidative Stress.

Plants have long been used in traditional medicine to treat illnesses. Nevertheless, their chemical diversity requires studies to establish the extract dosage and its safe use. Pseudobombax parvifolium, an endemic species of the Brazilian Caatinga biome, is commonly used in folk medicine, due to its anti-inflammatory properties related to cellular oxidative stress; however, its biological properties have scarcely been studied. In this study, we chemically characterized the P. parvifolium hydroalcoholic bark extract (EBHE) and evaluated its cytotoxic, mutagenic, and preclinical aspects, as well as its antioxidant effect. Our phytochemical analysis revealed a significative total polyphenol content and identified loliolide for the first time in this species. Cytotoxicity, mutagenicity, and acute oral and repeated dose indicated no toxic effects on cell culture, Drosophila melanogaster, and Wistar rat exposure to different EBHE concentrations, respectively. Furthermore, we observed a significant decrease in lipid peroxidation and a mild hypoglycemic and hypolipidemic effect with repeated oral dosing of EBHE. Although there were no significant changes in glutathione content, we did observe a significant increase in superoxide dismutase at a dose of 400 mg/kg and in glutathione peroxidase at doses of 100, 200, and 400 mg/kg. These findings suggest that EBHE has potential as a source of bioactive molecules, and it can be used safely in traditional medicine and in the development of herbal medicines for application in the public health system.

Low-energy amplitude-modulated electromagnetic field exposure: Feasibility study in patients with hepatocellular carcinoma.

BACKGROUND: Patients with advanced hepatocellular carcinoma (HCC) and poor liver function lack effective systemic therapies. Low-energy electromagnetic fields (EMFs) can influence cell biological processes via non-thermal effects and may represent a new treatment option. METHODS: This single-site feasibility trial enrolled patients with advanced HCC, Child-Pugh A and B, Eastern Cooperative Oncology Group 0-2. Patients underwent 90-min amplitude-modulated EMF exposure procedures every 2-4 weeks, using the AutEMdev (Autem Therapeutics). Patients could also receive standard care. The primary endpoints were safety and the identification of hemodynamic variability patterns. Exploratory endpoints included health-related quality of life (HRQoL), overall survival (OS). and objective response rate (ORR) using RECIST v1.1. RESULTS: Sixty-six patients with advanced HCC received 539 AutEMdev procedures (median follow-up, 30 months). No serious adverse events occurred during procedures. Self-limiting grade 1 somnolence occurred in 78.7% of patients. Hemodynamic variability during EMF exposure was associated with specific amplitude-modulation frequencies. HRQoL was maintained or improved among patients remaining on treatment. Median OS was 11.3 months (95% confidence interval [CI]: 6.0, 16.6) overall (16.0 months [95% CI: 4.4, 27.6] and 12.0 months [6.4, 17.6] for combination therapy and monotherapy, respectively). ORR was 24.3% (32% and 17% for combination therapy and monotherapy, respectively). CONCLUSION: AutEMdev EMF exposure has an excellent safety profile in patients with advanced HCC. Hemodynamic alterations at personalized frequencies may represent a surrogate of anti-tumor efficacy. NCT01686412.

Overexpression of a Short Sulfonylurea Splice Variant Increases Cardiac Glucose Uptake and Uncouples Mitochondria by Regulating ROMK Activity.

The mitochondrial splice variant of the sulfonylurea receptor (SUR2A-55) is associated with protection from myocardial ischemia-reperfusion (IR) injury, increased mitochondrial ATP sensitive K+ channel activity (mitoKATP) and altered glucose metabolism. While mitoKATP channels composed of CCDC51 and ABCB8 exist, the mitochondrial K+ pore regulated by SUR2A-55 is unknown. We explored whether SUR2A-55 regulates ROMK to form an alternate mitoKATP. We assessed glucose uptake in mice overexpressing SUR2A-55 (TGSUR2A-55) compared with WT mice during IR injury. We then examined the expression level of ROMK and the effect of ROMK modulation on mitochondrial membrane potential (Δψm) in WT and TGSUR2A-55 mice. TGSUR2A-55 had increased glucose uptake compared to WT mice during IR injury. The expression of ROMK was similar in WT compared to TGSUR2A-55 mice. ROMK inhibition hyperpolarized resting cardiomyocyte Δψm from TGSUR2A-55 mice but not from WT mice. In addition, TGSUR2A-55 and ROMK inhibitor treated WT isolated cardiomyocytes had enhanced mitochondrial uncoupling. ROMK inhibition blocked diazoxide induced Δψm depolarization and prevented preservation of Δψm from FCCP perfusion in WT and to a lesser degree TGSUR2A-55 mice. In conclusion, cardio-protection from SUR2A-55 is associated with ROMK regulation, enhanced mitochondrial uncoupling and increased glucose uptake.

Investigação de surto de doença compatível com escorbuto em uma penitenciária masculina do Ceará, 2019-2020: um estudo de caso-controle / Investigation of an outbreak of disease compatible with scurvy in a male penitentiary in the state of Ceará, Brazil, 2019-2020: a case-control study / Investigación de un brote de enfermedad compatible con escorbuto en una penitenciaría masculina en el estado de Ceará, Brasil, 2019-2020: un estudio de casos y controlesInvestigação de surto

Objetivo: identificar ocorrência de surto compatível com escorbuto e fatores de exposição associados aos sinais/sintomas típicos de hipovitaminose, em penitenciária masculina, Ceará, Brasil, 2019-2020. Métodos: estudo de caso-controle populacional; foram utilizados registros clínicos e entrevistas com casos compatíveis - sinais/sintomas iniciados no período - e com controles; realizou-se análise multivariável. Resultados: 62 casos; idade média de 40,6 anos (DP = 10,8); principais sinais/sintomas foram edema e dor em membros inferiores (100,0%), dificuldade para deambular (91,9%), hematoma/equimose em membros inferiores (90,3%), febre (88,7%); identificou-se, como fator de exposição, média de idade > 40 anos (ORa = 1,10; IC95% 1,05;1,17; p-valor = 0,001); e como fatores protetores, trabalho (ORa = 0,11; IC95% 0,03;0,36; p-valor < 0,001) e participação em aulas (ORa = 0,21; IC95% 0,08;0,59; p-valor = 0,003) dentro da penitenciária. Conclusão: surto da penitenciária compatível com escorbuto pelos sinais/sintomas característicos, associados aos fatores identificados; recomendou-se oferta regular de dieta rica em vitamina C para todos os internos e acompanhamento clínico dos casos.

Objective: to identify the occurrence of an outbreak compatible with scurvy and exposure factors associated with typical signs/symptoms of hypovitaminosis that occurred in a male penitentiary in Ceará, Brazil between 2019-2020. Methods: this was a population-based case-control study; we used clinical records and interviews with compatible cases - based on sign/symptom onset during the study period - and with controls; we carried out multivariate analysis. Results: out of 62 cases, mean age was 40.6 years (SD = 10.8); main signs/symptoms were edema and pain in the lower limbs (100.0%), difficulty in walking (91.9%), hematoma/ecchymosis in the lower limbs (90.3%) and fever (88.7%); we identified being over 40 years old as an associated factor (aOR = 1.10; 95%CI 1.05;1.17; p-value = 0.001); and as protective factors: working (aOR = 0.11; 95%CI 0.03;0.36; p-value < 0.001) and taking part in classes (aOR = 0.21; 95%CI 0.08;0.59; p-value = 0.003) in the prison. Conclusion: we considered the penitentiary outbreak to be compatible with scurvy due to characteristic signs/symptoms, associated with the identified factors; we recommended regular provision of a diet rich in vitamin C to all male inmates and clinical follow-up of cases.

Objetivo: identificar la ocurrencia del brote compatible con escorbuto y los factores de exposición asociados con signos/síntomas típicos de hipovitaminosis que ocurrieron en una penitenciaría masculina en Ceará, Brasil entre 2019-2020. Métodos: estudio poblacional de casos y controles; se utilizaron historias clínicas y entrevistas con casos compatibles, con inicio de signos/síntomas durante el período de estudio, y controles; se realizó análisis multivariable. Resultados: de los 62 casos, edad media fue 40,6 años (DE = 10,8); principales signos/síntomas fueron edema y dolor en miembros inferiores (100,0%), dificultad para caminar (91,9%), hematoma/equimosis en miembros inferiores (90,3%) y fiebre (88,7%); la edad mayor de 40 años se identificó como factor asociado (ORa = 1,10; IC95% 1,05;1,17; p-valor = 0,001); y como factores protectores: trabajo (ORa = 0,11; IC95% 0,03;0,36; p-valor< 0,001) y participación en clases (ORa = 0,21; IC95% 0,08;0,59; p-valor = 0,003) dentro del centro penitenciario. Conclusión: el brote en centro penitenciario fue considerado compatible con escorbuto debido a los signos/síntomas característicos, asociados a los factores identificados; se recomendó oferta regular de dieta rica en vitamina C a todos los internos y seguimiento clínico de los casos.

Capacitação para o controle da hanseníase: avaliação e contribuições para a gestão / Training process for leprosy control: evaluation and contributions to management

RESUMO Este estudo tem o objetivo de apresentar a avaliação de um projeto de capacitação em serviço para profissionais de saúde nas ações de prevenção e controle da hanseníase, problematizando o modelo de avaliação adotado, com foco na utilização para a gestão em saúde. Foi realizada uma avaliação ex-post em 18 municípios prioritários brasileiros participantes das capacitações. Empregou-se a estratégia Rapid Evaluation Methods (REM), priorizando: a) abordagem colaborativa; b) técnicas qualitativas; e c) enfoque conceitual da translação do conhecimento. Foram realizadas 24 entrevistas grupais, envolvendo 278 participantes. A abordagem de ensino em serviço foi importante para revalorização das ações de prevenção e controle da hanseníase e para conferir um lugar privilegiado de discussão técnica, de reflexão e de mudanças na atenção primária e em sua relação com a especializada. Conclui-se que o modelo de avaliação possibilitou que as controvérsias e convergências surgissem, assim como as recomendações para ajustes da intervenção junto à gestão em tempo oportuno.

ABSTRACT This study aims to present the evaluation of an in-service training project for health professionals in leprosy prevention and control actions, questioning the adopted evaluation model, focusing on its use for health management. An ex-post evaluation was carried out in 18 priority Brazilian municipalities participating in the training project. Rapid Evaluation Methods (REM) strategy was employed, prioritizing: a) a collaborative approach; b) qualitative techniques; and c) a conceptual approach to knowledge translation. Twenty-four group interviews were carried out, involving 278 participants. The in-service teaching approach was important for revaluing leprosy prevention and control actions and to provide a privileged place for technical discussion, reflection and changes in primary health care and in its relationship with specialized care. It can be concluded that the evaluation model enabled controversies and convergences to emerge, as well as recommendations for managers to adjust the intervention timely.

Overview of general surgery medical residency programs and prerequisite program in basic surgical area in Brazil: Historical review and update.

OBJECTIVE: to describe vacancy regulation process by adding, describing the panorama of the General Surgery Residency Program (PRMCG) and the Basic Surgical Prerequisites Program (PRACB). METHOD: descriptive, quali-quantitative, cross sectional study conducted from document analysis from National Commission of Medical Residency (CNRM). RESULTS: in 2018, after evaluation of the General Surgery Services for adequacy of the number of vacancies (DS), the PRACB was instituted as a modality of access to surgical specialties until definitive change in the time of the formation of the general surgeon for three years, in 2022. In the first addition of vacancies in 2018, 127 PRMCG were authorized with 736 vacancies of R1 and 290 PRACB (2 years) with 1.286 vacancies offered for R1. In the second addition in 2021, 423 PRM were authorized with 1.564 R1 vacancies in PRMCG. DISCUSSION: the regulation of the offer of vacancies for the formation of specialties in Brazil should align the evaluation of practice scenarios with the profile of skills. The PRACB modality was instituted for a certain time for budgetary preparation and practice scenarios until the complete transition to training in 3 years. CONCLUSION: Brazil by 2018 was the only country to grant the Board Certification to General Surgeon with only 2 years of training. After a transitional period the same analysis methodology for adding and regulating vacancies was applied to services.

Aggression Towards Caregivers in Parkinson's Disease and Related Disorders: A Mixed Methods Study.

Background: Aggression is one manifestation of behavioral disturbances in neurodegenerative disease with emerging literature suggesting a high prevalence in Parkinson's disease and related disorders (PDRD). Objectives: Our aim was to describe characteristics, associated factors, and consequences of aggression towards caregivers in PDRD. Methods: This is a convergent mixed methods study, leveraging data from 296 PDRD patient-caregiver dyads in a clinical trial of palliative care and semi-structured interviews with a subgroup of 14 caregivers who reported aggression. The primary outcome was baseline caregiver-reported aggression. Using multivariate linear regression, baseline dyad characteristics (eg, measures of disease, psychosocial issues, caregiver strain) were examined to identify factors associated with aggression. Thematic analysis of interviews was used to augment these findings. Results: Associated variables included disease duration (r = 0.15, P < 0.05), patient grief (r = 0.22, P< 0.001), symptom burden (r = 0.18, r < 0.01), resistance to care (r = 0.40, P < 0.01), caregivers' depression (r = 0.16, P < 0.05), and caregiving burden (r = 0.34, P < 0.001). We identified five themes: (1) Aggressive behaviors range from verbal abuse to threats of physical violence; (2) Caregivers believe that aggressive behaviors result from the difficulty patients experience in coping with disease progression and related losses; (3) Caregivers' stress and mental health are worsened by aggressive behaviors; (4) Aggressive behaviors negatively affect patient-caregiver relationships; (5) Caregivers are ill-prepared to manage aggressive behaviors and cope with the consequences on their own. Conclusions: Aggression in PDRD is driven by diverse factors (eg, grief, fluctuations in cognition) with serious consequences for caregivers. Neurologists and movement specialists should consider screening for aggression while prioritizing caregiver education and wellbeing.

Light induces peridinin and docosahexaenoic acid accumulation in the dinoflagellate Durusdinium glynnii.

Peridinin is a light-harvesting carotenoid present in phototrophic dinoflagellates and has great potential for new drug applications and cosmetics development. Herein, the effects of irradiance mediated by light-emitting diodes on growth performance, carotenoid and fatty acid profiles, and antioxidant activity of the endosymbiotic dinoflagellate Durusdinium glynnii were investigated. The results demonstrate that D. glynnii is particularly well adapted to low-light conditions; however, it can be high-light-tolerant. In contrast to other light-harvesting carotenoids, the peridinin accumulation in D. glynnii occurred during high-light exposure. The peridinin to chlorophyll-a ratio varied as a function of irradiance, while the peridinin to total carotenoids ratio remained stable. Under optimal irradiance for growth, there was a peak in docosahexaenoic acid (DHA) bioaccumulation. This study contributes to the understanding of the photoprotective role of peridinin in endosymbiont dinoflagellates and highlights the antioxidant activity of peridinin-rich extracts. KEY POINTS: • Peridinin has a protective role against chlorophyll photo-oxidation • High light conditions induce cellular peridinin accumulation • D. glynnii accumulates high amounts of DHA under optimal light supply.

In silico and in vitro structure-stability-function relationship of analog peptides of Stigmurin and its antibacterial and antibiofilm activities.

Multidrug-resistant bacterial infections are a threat to public health worldwide, which boosts the urgent need for pharmacological research for new drugs. Although the peptides without disulfide bridges from scorpions have shown antimicrobial action, usually their toxicity hamper their pharmacological application. Stigmurin is a non-hemolytic cationic peptide from Tityus stigmurus venom with antibacterial effect and toxicity on normal cells. In this approach, the conformational changes and stability of two Stigmurin analog peptides, named StigA8 and StigA18, were evaluated by circular dichroism, as well as the mechanism of interaction with bacterial membranes in silico. In addition, the in vitro and in vivo antibacterial activity and the action against the biofilm formed by multidrug-resistant Staphylococcus aureus were investigated. StigA8 (+4) and StigA18 (+5) revealed the ability to change their structural conformation depending on the medium composition, and high stability at different temperatures and pH conditions. Both analog peptides showed greater ability to interact with bacterial membranes in silico when compared to the native one. StigA8 and StigA18 demonstrated low hemolytic action, with non-toxic effect on G. mellonella larvae up to 120 mg/kg. StigA8 and StigA18 presented a broad spectrum of antibacterial action in vitro, especially against multidrug-resistant clinical isolates. The analog peptides (7.5 µM) also reduced the biofilm biomass of multidrug-resistant S. aureus, as well as increased the larval survival of the Galleria mellonella infected larvae. Therefore, StigA8 and StigA18 showed a beneficial potential in the treatment of bacterial infections, constituting promising bioactive components for the development of new antimicrobial agents.

MedMinas project: design and use of mixed methods in the evaluation of pharmaceutical services in primary health care in Minas Gerais, Brazil.

BACKGROUND: The main purposes of primary care-based pharmaceutical services (PHCPS) in Brazil are to provide free access to medicines and pharmaceutical care to patients. Several obstacles hinder achieving their goals; thus, MedMinas Project aimed to evaluate the PHCPS, the supply system, and the use of medicines. This paper reflects on our experience designing, planning, and conducting the project, describing the issues yielded in the field and lessons learned. METHODS: This work consists of a mixed-methods study conducted in Minas Gerais, Southeastern Brazil. We adopted the principles of Rapid Evaluation Methods, employing a multistage stratified sampling for the quantitative and a purposeful sampling for the qualitative components, respectively, and a documentary research. Data sources included individuals (patients and professionals), prescriptions, dispensed medicines, and policy documents collected between April and October 2019. The quantitative data described in this paper were analysed by descriptive statistics and the qualitative by Thematic Content Analysis. RESULTS: A total of 26 municipalities varying from 37,784 to 409,341 inhabitants were included. The field team spent, on average, 16 days in each location. We interviewed 1019 respondents, of which 127 were professionals and 892 patients. The participation rate varied from 92 to 100%, depending on the respondent subgroup. Most interviews lasted between 45 min and one hour. Fieldwork challenges included participants' enrolment, field team, interview processes, and project budget. The participants provided positive feedback and five main themes emerged from the interview experience (self-awareness, sense of gratitude, research value, access to findings, and benefits of the research). Additionally, we collected copies of 1072 documents and 2070 pieces of data from prescriptions filled and medicines dispensed at the PCP. CONCLUSION: We demonstrated the viability of conducting the MedMinas Project in an extensive geographic area within effective time frames that provided meaningful, high-quality data from multiple actors. The methods and lessons learned are valuable for researchers across various disciplines in similar urban settings in Brazil and other countries of low- and middle-income (LMIC).

Models of Electron Transfer at Different Electrode Materials.

Electron transfer is the most important electrochemical process. In this review, we present elements of various aspects of electron transfer theory from the early work of Marcus and Hush to recent developments. The emphasis is on the role of the electronic, and to a lesser extent the geometrical, properties of the electrode. A variety of experimental works are discussed in light of these theoretical concepts. Because the field of electron transfer is so vast, this review is far from comprehensive; rather, we focus on systems that offer a special interest and illuminate aspects of the theory.