Novel pesticides design: co-encapsulation of citral and cyproconazole for the control of Botrytis cinerea using biocompatible nano-carriers.

BACKGROUND: Growing concerns about sustainability have driven the search for eco-friendly pest management solutions. Combining natural and synthetic compounds within controlled release systems is a promising strategy. This study investigated the co-encapsulation of the natural compound citral (Cit) and the synthetic antifungal cyproconazole (CPZ) using two water-based nanocarriers: solid lipid nanoparticles (SLNs) and chitosan nanoparticles (CSNPs). RESULTS: Both CSNPs and SLNs loaded with Cit + CPZ displayed superior antifungal activity against Botrytis cinerea compared to free compounds. Notably, CSNPs with a 2:1 Cit:CPZ ratio exhibited the highest efficacy, achieving a minimum inhibitory concentration (MIC100) of < 1.56 µg mL-1, lower than the 12.5 µg mL-1 of non-encapsulated compounds. This formulation significantly reduced the required synthetic CPZ while maintaining efficacy, highlighting its potential for environmentally friendly pest control. CONCLUSION: The successful co-encapsulation of Cit + CPZ within CSNPs, particularly at a 2:1 ratio, demonstrates a promising approach for developing effective and sustainable antifungal formulations against B. cinerea. © 2024 Society of Chemical Industry.

Heart Disease in Mothers of Children with Duchenne Muscular Dystrophy.

Female carriers of Duchenne Muscular Dystrophy (DMD) carry a heterozygous pathogenic variant in the dystrophin gene and can transmit pathogenic variants to their offspring. DMD is an X-linked recessive disease that affects up to 19.8 in every 100,000 male births. Those carriers with symptoms can be referred to as women with dystrophinopathy. Even among asymptomatic carriers, cardiac involvement can be verified in between 2.5% and 75% through echocardiography. The most commonly affected wall of the left ventricle is the inferolateral, with myocardial fibrosis detected by cardiac nuclear resonance. Therefore, screening is recommended for these women carriers due to the risk of cardiomyopathy. There is a lack of longitudinal studies on the evolution of these carriers. In this article, data on clinical presentation, cardiac assessment for female patients with dystrophinopathy and DMD carriers, and approaches for these patients are discussed.

Bioprospecting, Synergistic Antifungal and Toxicological Aspects of the Hydroxychalcones and Their Association with Azole Derivates against Candida spp. for Treating Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) remains a prevalent fungal disease, characterized by challenges, such as increased fungal resistance, side effects of current treatments, and the rising prevalence of non-albicans Candida spp. naturally more resistant. This study aimed to propose a novel therapeutic approach by investigating the antifungal properties and toxicity of 2-hydroxychalcone (2-HC) and 3'-hydroxychalcone (3'-HC), both alone and in combination with fluconazole (FCZ) and clotrimazole (CTZ). A lipid carrier (LC) was also developed to deliver these molecules. The study evaluated in vitro anti-Candida activity against five Candida species and assessed cytotoxicity in the C33-A cell line. The safety and therapeutic efficacy of in vivo were tested using an alternative animal model, Galleria mellonella. The results showed antifungal activity of 2-HC and 3'-HC, ranging from 7.8 to 31.2 as fungistatic and 15.6 to 125.0 mg/L as fungicide effect, with cell viability above 80% from a concentration of 9.3 mg/L (2-HC). Synergistic and partially synergistic interactions of these chalcones with FCZ and CTZ demonstrated significant improvement in antifungal activity, with MIC values ranging from 0.06 to 62.5 mg/L. Some combinations reduced cytotoxicity, achieving 100% cell viability in many interactions. Additionally, two LCs with suitable properties for intravaginal application were developed. These formulations demonstrated promising therapeutic efficacy and low toxicity in Galleria mellonella assays. These results suggest the potential of this approach in developing new therapies for VVC.

Development of a Versatile Nanostructured Lipid Carrier (NLC) Using Design of Experiments (DoE)-Part II: Incorporation and Stability of Butamben with Different Surfactants.

Nanostructured lipid carriers (NLCs) are typically composed of liquid lipids, solid lipids, and surfactants, enabling the encapsulation of lipophilic drugs. Butamben is a Class II anesthetic drug, according to the Biopharmaceutical Classification System (BCS); it has a log P of 2.87 and is considered a 'brick dust' (poorly water-soluble and poorly lipid-soluble) drug. This characteristic poses a challenge for the development of NLCs, as they are not soluble in the liquid lipid present in the NLC core. In a previous study, we developed an NLC core consisting of a solid lipid (CrodamolTM CP), a lipophilic liquid with medium polarity (SRTM Lauryl lactate), and a hydrophilic excipient (SRTM DMI) that allowed the solubilization of 'brick dust' types of drugs, including butamben. In this study, starting from the NLC core formulation previously developed we carried out an optimization of the surfactant system and evaluated their performance in aqueous medium. Three different surfactants (CrodasolTM HS HP, SynperonicTM PE/F68, and CroduretTM 40) were studied and, for each of them, a 23 factorial design was stablished, with total lipids, % surfactant, and sonication time (min) as the input variables and particle size (nm), polydispersity index (PDI), and zeta potential (mV) as the response variables. Stable NLCs were obtained using CrodasolTM HS HP and SynperonicTM PE/F68 as surfactants. Through a comparison between NLCs developed with and without SRTM DMI, it was observed that besides helping the solubilization of butamben in the NLC core, this excipient helped in stabilizing the system and decreasing particle size. NLCs containing CrodasolTM HS HP and SynperonicTM PE/F68 presented particle size values in the nanometric scale, PDI values lower than 0.3, and zeta potentials above |10|mV. Concerning NLCs' stability, SBTB-NLC with SynperonicTM PE/F68 and butamben demonstrated stability over a 3-month period in aqueous medium. The remaining NLCs showed phase separation or precipitation during the 3-month analysis. Nevertheless, these formulations could be freeze-dried after preparation, which would avoid precipitation in an aqueous medium.

Bioactivity and Bioavailability of Carotenoids Applied in Human Health: Technological Advances and Innovation.

This article presents a groundbreaking perspective on carotenoids, focusing on their innovative applications and transformative potential in human health and medicine. Research jointly delves deeper into the bioactivity and bioavailability of carotenoids, revealing therapeutic uses and technological advances that have the potential to revolutionize medical treatments. We explore pioneering therapeutic applications in which carotenoids are used to treat chronic diseases such as cancer, cardiovascular disease, and age-related macular degeneration, offering novel protective mechanisms and innovative therapeutic benefits. Our study also shows cutting-edge technological innovations in carotenoid extraction and bioavailability, including the development of supramolecular carriers and advanced nanotechnology, which dramatically improve the absorption and efficacy of these compounds. These technological advances not only ensure consistent quality but also tailor carotenoid therapies to each patient's health needs, paving the way for personalized medicine. By integrating the latest scientific discoveries and innovative techniques, this research provides a prospective perspective on the clinical applications of carotenoids, establishing a new benchmark for future studies in this field. Our findings underscore the importance of optimizing carotenoid extraction, administration, bioactivity, and bioavailability methods to develop more effective, targeted, and personalized treatments, thus offering visionary insight into their potential in modern medical practices.

Fresh Carrier for an Old Topical Local Anesthetic: Benzocaine in Nanostructured Lipid Carriers.

Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.

Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping.

The objective of this study was to develop a versatile lipid core for the 'brick-dust type of drugs' (poorly water-soluble and poorly lipid-soluble drugs). In the first step, excipients of different polarities were classified according to their behavior in aqueous solutions. Subsequently, binary mixtures were prepared with cetyl palmitate (Crodamol™ CP pharma, Campinas, São Paulo, Brazil) as the solid lipid, and its miscibility with other excipients was evaluated using Raman mapping and classical least squares (CLS). Based on the results, the excipients Crodamol™ CP pharma (hydrophobic), Super Refined™ DMI (dimethyl isosorbide; hydrophilic, Mill Hall, PA, USA), and Super Refined™ Lauryl Lactate (lauryl lactate, medium polarity, Mill Hall, PA, USA) were chosen to compose the lipid core. The ideal proportion of these excipients was determined using a mixture design and the standard deviation (STD) of image histograms as the response variables. After statistical evaluation of the DoE results, the final composition was determined, and drugs with different logP (0 to 10) and physicochemical characteristics were evaluated in the optimized mixture. The drugs butamben (Sigma-Aldrich Co., Spruce Street, St. Louis, MO, USA), tacrolimus (NutriFarm, São Paulo, Brazil), atorvastatin calcium, and resveratrol (Botica da Terra, Campinas, Brazil) presented a homogeneous distribution in the optimized lipid core, indicating that this is a promising system to be used in nanostructured lipid carrier (NLC) formulations of such types of drugs.

Sonoprocessing enhances the stabilization of fisetin by encapsulation in Saccharomyces cerevisiae cells.

The objective of this study was to investigate for the first time the role of S. cerevisiae natural barriers and endogenous cytoplasmatic bodies on the stabilization of fisetin encapsulated via sonoprocessing coupled to freeze-drying (FD) or spray drying (SD). Both protocols of encapsulation improved the resistance of fisetin against thermal treatments (between 60 and 150 °C) and photochemical-induced deterioration (light exposition for 60 days) compared to non-encapsulated fisetin (antioxidant activity retention of approximately 55% and 90%, respectively). When stored under constant relative humidity (from 32.8 to 90%) for 60 days, yeast carriers improved the half-life time of fisetin by up to 4-fold. Spray dried particles were smaller (4.9 µm) and showed higher fisetin release after simulated gastrointestinal digestion (55.7%) when compared to FD. Freeze-dried particles, in turn, tended to agglomerate more than SD (zeta potential -19.7 mV), resulting in reduced loading features (6.3 mg/g) and less efficient protection of fisetin to heat, photo, and moisture-induced deterioration. Overall, spray-dried sonoprocessed fisetin capsules are an efficient way to preserve fisetin against harsh conditions. Altogether, this report shows that sonoprocessing coupled to drying is an efficient, creative, and straightforward route to protect and deliver lipophilic fisetin using yeast capsules for food applications.

Application of nano-antibiotics in the diagnosis and treatment of infectious diseases / Aplicação de nanoantibióticos no diagnóstico e tratamento de doenças infecciosas

Infectious diseases are the leading cause of death worldwide. Thus, nanotechnology provides an excellent opportunity to treat drug-resistant microbial infections. Numerous antibiotics have been used to inhibit the growth and kill of microbes, but the development of resistance and the emergence of side effects have severely limited the use of these agents. Due to the development of the nanotechnology, nanoparticles are widely used as antimicrobials. Silver and chitosan nanoparticles have antifungal, antiviral and antibacterial properties, and many studies confirm the antifungal properties of silver nanoparticles. Nowadays, the use of nanoparticles in the diagnosis and treatment of infectious diseases has developed due to less side effects and also the help of these particles in effective drug delivery to the target tissue. Liposomes are also used as carriers of drug delivery, genes, and modeling of cell membranes in both animals and humans. The ability of these liposomes to encapsulate large amounts of drugs, minimize unwanted side effects, high effectiveness and low toxicity has attracted the interest of researchers. This review article examines recent efforts by researchers to identify and treat infectious diseases using antimicrobial nanoparticles and drug nano-carriers.

As doenças infecciosas são a principal causa de morte no mundo. Assim, a nanotecnologia oferece uma excelente oportunidade para tratar infecções microbianas resistentes a medicamentos. Numerosos antibióticos têm sido usados para inibir o crescimento e a morte de micróbios, mas o desenvolvimento de resistência e o surgimento de efeitos colaterais limitaram severamente o uso desses agentes. Devido ao desenvolvimento da nanotecnologia, as nanopartículas são amplamente utilizadas como antimicrobianos. As nanopartículas de prata e quitosana têm propriedades antifúngicas, antivirais e antibacterianas, e muitos estudos confirmam as propriedades antifúngicas das nanopartículas de prata. Atualmente, o uso de nanopartículas no diagnóstico e tratamento de doenças infecciosas tem se desenvolvido em razão do menor número de efeitos colaterais e também à ajuda dessas partículas na efetiva entrega de fármacos ao tecido-alvo. Os lipossomas também são usados como transportadores de entrega de drogas, genes e modelagem de membranas celulares em animais e humanos. Os lipossomas também são usados como transportadores de entrega de drogas, genes e modelagem de membranas celulares em animais e humanos. A capacidade desses lipossomas de encapsular grandes quantidades de fármacos, minimizar efeitos colaterais indesejados, alta eficácia e baixa toxicidade tem despertado o interesse de pesquisadores. Este artigo de revisão examina esforços recentes de pesquisadores para identificar e tratar doenças infecciosas usando nanopartículas antimicrobianas e nanotransportadores de drogas.

Detecting Residual Chronic Salmonella Typhi Carriers on the Road to Typhoid Elimination in Santiago, Chile, 2017-2019.

BACKGROUND: In Santiago, Chile, where typhoid had been hyperendemic (1977-1991), we investigated whether residual chronic carriers could be detected among household contacts of non-travel-related typhoid cases occurring during 2017-2019. METHODS: Culture-confirmed cases were classified as autochthonous (domestically acquired) versus travel/immigration related. Household contacts of cases had stool cultures and serum Vi antibody measurements to detect chronic Salmonella Typhi carriers. Whole genome sequences of acute cases and their epidemiologically linked chronic carrier isolates were compared. RESULTS: Five of 16 autochthonous typhoid cases (31.3%) were linked to 4 chronic carriers in case households; 2 cases (onsets 23 months apart) were linked to the same carrier. Carriers were women aged 69-79 years with gallbladder dysfunction and Typhi fecal excretion; 3 had highly elevated serum anti-Vi titers. Genomic analyses revealed close identity (≤11 core genome single-nucleotide polymorphism [SNP] differences) between case and epidemiologically linked carrier isolates; all were genotypes prevalent in 1980s Santiago. A cluster of 4 additional autochthonous cases unlinked to a carrier was identified based on genomic identity (0-1 SNPs). Travel/immigration isolate genotypes were typical for the countries of travel/immigration. CONCLUSIONS: Although autochthonous typhoid cases in Santiago are currently rare, 5 of 16 such cases (31.3%) were linked to elderly chronic carriers identified among household contacts of cases.

Impacto del Programa de prevención de anemia por hematíes falciformes

Introducción: la anemia de células falciformes es una enfermedad genética autosómica recesiva considerada la enfermedad hereditaria más frecuente en Cuba. El Programa Cubano de prevención de anemia por hematíes falciformes, se basa en el pesquisaje mediante estudio de electroforesis de hemoglobina a todas las gestantes, el cual es aplicado desde el año 1983. Objetivo: describir el impacto del Programa Cubano de prevención de anemia por hematíes falciformes en Granma, en el período de 1987-2021. Métodos: se realizó un estudio observacional, ambipestivo, de serie de casos en las gestantes pertenecientes a la provincia Granma en el período 1987-2021. Se revisaron las estadísticas de los departamentos municipales y provincial. Se analizaron las variables como frecuencia de portadoras, variantes de hemoglobina, cobertura de esposos estudiados, diagnóstico prenatal molecular y casos positivos. Para el análisis estadístico se emplearon medidas de resumen como frecuencias absolutas y relativas. Resultados: se comprobó que la frecuencia de portadoras de la provincia es de 3,9 %. La variante más frecuente es la Hb AS. Se estudiaron 62 % de los esposos. Se realizó el 70,3 % de los diagnósticos moleculares, de los cuales 21,3 % fue positivo optando por la terminación voluntaria de la gestación en el 69 % de ellos. Conclusiones: se logró impacto del Programa Cubano de prevención de anemia por hematíes falciformes en el período de 1987-2021 en cuanto a la detección de portadoras de la enfermedad, frecuencia de diagnósticos prenatales moleculares, enfermos e interrupciones por esta causa.

Introduction: Sickle cell anemia is an autosomal recessive genetic disease. It is considered the most common hereditary disease in Cuba. The Cuban sickle cell anemia prevention Program is based on the screening of all pregnant women by hemoglobin electrophoresis. This program has been applied since 1983. Objective: To describe the impact of the Cuban sickle cell anemia prevention Program during the period 1987-2021. Methods: An observational study was conducted on a series of cases of pregnant women belonging to the province of Granma in the period from 1987 to 2021. Municipal and provincial statistics were reviewed. Variables such as carrier frequency, hemoglobin variants, coverage of studied spouses, molecular prenatal diagnosis, and positive cases were analyzed. Summary measures such as absolute and relative frequencies were used for statistical analysis. Results: The carrier frequency in the province was found to be 3.9%. The most common variant is Hb AS. Sixty-two percent of spouses were screened. Molecular diagnosis was performed in 70.3%, of which 21.3% were positive and 69% opted for voluntary abortion. Conclusions: The Cuban Sickle Cell Disease Prevention Program has had a great impact on halting the number of carriers of the disease, the frequency of prenatal molecular diagnoses, and the number of patients with sickle cell anemia in the period 1987-2021.

Introdução: A anemia falciforme é uma doença genética autossómica recessiva, sendo considerada a doença hereditária mais comum em Cuba. O programa cubano de prevenção da anemia falciforme baseia-se no rastreio de todas as mulheres grávidas através da eletroforese da hemoglobina, que tem sido aplicado desde 1983. Objetivo: Descrever o impacto do Programa Cubano de Prevenção da Anemia Falciforme durante o período 1987-2021. Métodos: Foi realizado um estudo observacional de uma série de casos de mulheres grávidas pertencentes à província de Granma no período de 1987 a 2021. Foram revistas estatísticas municipais e provinciais. Foram analisadas variáveis como frequência de portadores, variantes de hemoglobina, cobertura de cônjuges estudados, diagnóstico pré-natal molecular e casos positivos. Para a análise estatística foram utilizadas medidas de síntese como frequências absolutas e relativas. Resultados: A frequência de portadores na província foi de 3,9%. A variante mais comum é a Hb AS. Sessenta e dois por cento dos cônjuges foram rastreados. O diagnóstico molecular foi efectuado em 70,3%, dos quais 21,3% foram positivos e 69% optaram pelo aborto voluntário. Conclusões: O Programa Cubano de Prevenção da Doença Falciforme teve um grande impacto na redução do número de portadores da doença, na frequência dos diagnósticos moleculares pré-natais e no número de pacientes com anemia falciforme no período 1987-2021.

Nanostructured Lipid Carriers as Robust Systems for Lupeol Delivery in the Treatment of Experimental Visceral Leishmaniasis.

Leishmaniasis is a neglected tropical disease that affects millions of people around the world. Available therapy causes severe side effects, has unacceptable prices for some specific formulations, and the existence of drug-resistant parasites limits the use of the currently available arsenal of antiparasitic drugs. Therefore, natural products serve as one of the main sources to develop new and effective alternative drugs against leishmaniasis. In this sense, the present study evaluated the potential of the triterpene Lupeol (Lu) entrapped in nanostructured lipid carriers (NLCs) for the treatment of experimental visceral leishmaniasis. The therapeutic efficacy of Lu or Lu entrapped in NLC (Lu-NLC) was investigated in golden hamsters infected with Leishmania (Leishmania) infantum. Lu-NLC presented a mean particle size of 265.3 ± 4.6 nm, a polydispersity index of <0.25 and a zeta potential of -37.2 ± 0.84 mV; the efficacy of encapsulation was 84.04 ± 0.57%. Studies on hamsters showed that Lu-NLC (5 mg/kg) administered intraperitoneally for 10 consecutive days caused a reduction of 99.9% in the number of parasites in the spleen and liver compared to the untreated infected control. On the contrary, Lu-treated animals (5 mg/kg) had 94.4 and 90.2% less parasites in the spleen and liver, respectively, than the infected group. Additionally, a significant preservation of splenic and hepatic tissues was observed in animals treated with Lu-NLC or Lu. Furthermore, Lu-NLC-treated animals produced high levels of anti-Leishmania IgG2 isotype. These data indicate that NLC potentialized Lu efficacy in experimental visceral leishmaniasis. This work suggests that Lu and nanoformulations carrying this compound may be considered as an important tool to be included in the alternative therapy of leishmaniasis.

Microneedles for oral mucosal delivery - Current trends and perspective on future directions.

INTRODUCTION: Oral cavity drug and vaccine delivery has the potential for local targeting, dose reduction, minimization of systemic side effects, and generation of mucosal immunity. To overcome current limitations of delivery into the oral cavity mucosa, microneedles (MNs) have emerged as a promising technology. AREAS COVERED: We reviewed the literature on MN application in the oral cavity, including in vitro studies, in vivo animal studies, and human clinical trials. EXPERT OPINION: MNs are sufficiently robust to cross the oral cavity epithelium and nearly painless when applied to different parts of the human oral mucosa including the lip, cheek, tongue, and palate. In recent years, MNs have been evaluated for different applications, including vaccination, topical anesthetic delivery, and treatment of local oral pathologies such as oral lesions or carcinomas. MNs are attractive because they have the potential to produce a better treatment outcome with reduced side effects. Over the coming years, we project a significant increase in research related to the development of MNs for use in dentistry and other medical conditions of the mouth.

Successful treatment with streptomycin of genital leptospirosis in naturally infected cows under field conditions.

The single-dose protocol of streptomycin treatment has been recommended to treat renal leptospirosis in bovines. However, treating genital infection remains a challenge. Recently, a protocol using three doses of streptomycin demonstrated effectiveness in the genital clearance of experimentally infected ewes. Therefore, the present study aimed to apply this three-dose protocol for genital infection treatment in naturally infected cows under field conditions. Thirty beef cows were diagnosed as positive by lipL32-PCR in their genital samples. Nucleotide sequences (n = 10) characterized them as Leptospira interrogans sg Sejroe, genetically related to Hardjoprajitno strains. After molecular diagnosis, 13 cows received a single dose of 25 mg/kg streptomycin. The other 17 cows were submitted to the three-dose protocol. The successful treatment rate of genital infection on the single streptomycin dose was 7/13 (53.8%), while the cows that received the three doses 16/17 were negative (94.1% of efficacy). Based on those results, we conclude that the standard treatment preconized for renal infection is not adequate for genital infection, and the three-dose protocol was successful in eliminating the carrier status of genital leptospirosis.

Maximal Ratio Combining Detection in OFDM Systems with Virtual Carriers Over V2V Channels.

This paper examines the performance of orthogonal frequency division multiplexing (OFDM) systems for vehicle-to-vehicle (V2V) communication channels. More specifically, a doubly selective channel under high intercarrier interference (ICI) is considered. Current solutions involve complex detection and/or reduced spectral efficiency receivers. This paper proposes the use of virtual carriers (VC) in an OFDM system with a low-complexity maximal ratio combining (MRC) detector to improve the bit error rate (BER) performance. The results show that VC provides diversity in received data, resulting in a ≥5 dB gain compared to previous OFDM systems with conventional linear/nonlinear detectors used as a reference. The detector presented in this paper has linear complexity, making it a suitable solution for real-time V2V communication systems.

Molecular characterization and genotyping of isolates from cancer patients with Clostridioides difficile infection or asymptomatic colonization.

Introduction. Cancer patients with Clostridioides difficile infection (CDI) are at a higher risk for adverse outcomes. In addition, a high prevalence of Clostridioides difficile asymptomatic colonization (CDAC) has been reported in this vulnerable population.Gap Statement. The molecular characteristics and potential role of CDAC in healthcare-related transmission in the cancer population have been poorly explored.Aim. We aimed to compare the molecular and genotypic characteristics of C. difficile isolates from cancer patients with CDAC and CDI.Method. We conducted a prospective cohort study of cancer patients with CDAC or CDI from a referral centre. Molecular characterization, typification and tcdC gene expression of isolates were performed.Results. The hospital-onset and community-onset healthcare facility-associated CDI rates were 4.5 cases/10 000 patient-days and 1.4 cases/1 000 admissions during the study period. Fifty-one C. difficile strains were isolated: 37 (72 %) and 14 (28 %) from patients with CDI or CDAC, respectively. All isolates from symptomatic patients were tcdA+/tcdB+, and four (10 %) were ctdA+/ctdB+. In the CDAC group, 10 (71 %) isolates were toxigenic, and none were ctdA+/ctdB+. The Δ18 in-frame tcdC deletion and two transition mutations were found in five isolates. After bacterial typing, 60 % of toxigenic isolates from asymptomatic carriers were clonal to those from patients with C. difficile-associated diarrhoea. No NAP1/027/BI strains were detected.Conclusions. We found a clonal association between C. difficile isolates from patients with CDAC and CDI. Studies are needed to evaluate the potential role of asymptomatic carriers in the dynamics of nosocomial transmission to support infection control measures and reduce the burden of CDI in high-risk groups.

Interference with Bacterial Conjugation and Natural Alternatives to Antibiotics: Bridging a Gap.

Horizontal gene transfer (HGT) in food matrices has been investigated under conditions that favor gene exchange. However, the major challenge lies in determining the specific conditions pertaining to the adapted microbial pairs associated with the food matrix. HGT is primarily responsible for enhancing the microbial repertoire for the evolution and spread of antimicrobial resistance and is a major target for controlling pathogens of public health concern in food ecosystems. In this study, we investigated Salmonella Heidelberg (SH) and Escherichia coli (EC) regarding gene exchange under conditions mimicking the industrial environment, with the coproducts whey (SL) and chicken juice (CJ). The S. Heidelberg strain was characterized by antibiotic susceptibility standards and PCR to detect the blaTEM gene. A concentration of 0.39 mg/mL was determined to evaluate the anti-conjugation activity of nanostructured lipid nanocarriers (NLCs) of essential oils to mitigate ß-lactam resistance gene transfer. The results showed that the addition of these coproducts promoted an increase of more than 3.5 (whey) and 2.5 (chicken juice) orders of magnitude in the conjugation process (p < 0.01), and NLCs of sage essential oil significantly reduced the conjugation frequency (CF) by 74.90, 90.6, and 124.4 times when compared to the transfers in the absence of coproducts and the presence of SL and CJ, respectively. For NLCs from olibanum essential oil, the decrease was 4.46-fold for conjugations without inhibitors and 3.12- and 11.3-fold in the presence of SL and CJ. NLCs associated with sage and olibanum essential oils effectively control the transfer of antibiotic resistance genes and are a promising alternative for use at industrial levels.

Inhaled lipid nanocarriers for pulmonary delivery of glucocorticoids: Previous strategies, recent advances and key factors description.

In view of the strong anti-inflammatory activity of glucocorticoids (GC) they are used in the treatment of almost all inflammatory lung diseases. In particular, inhaled GC (IGC) allow high drug concentrations to be deposited in the lung and may reduce the incidence of adverse effects associated with systemic administration. However, rapid absorption through the highly absorbent surface of the lung epithelium may limit the success of localized therapy. Therefore, inhalation of GC incorporated into nanocarriers is a possible approach to overcome this drawback. In particular, lipid nanocarriers, which showed high pulmonary biocompatibility and are well known in the pharmaceutical industry, have the best prospects for pulmonary delivery of GC by inhalation. This review provides an overview of the pre-clinical applications of inhaled GC-lipid nanocarriers based on several key factors that will determine the efficiency of local pulmonary GC delivery: 1) stability to nebulization, 2) deposition profile in the lungs, 3) mucociliary clearance, 4) selective accumulation in target cells, 5) residence time in the lung and systemic absorption and 6) biocompatibility. Finally, novel preclinical pulmonary models for inflammatory lung diseases are also discussed.

Pneumococcal serotypes and antibiotic resistance in healthy carriage children after introduction of PCV13 in Lima, Peru.

OBJECTIVE: To determinate the frequency of Streptococcus pneumoniae nasopharyngeal carriers, serotypes and antimicrobial resistance in healthy children in Lima, Peru, post-PCV13 introduction and to compare the results with a similar study conducted between 2006 and 2008 before PCV7 introduction (pre-PCV7). METHODS: A cross-sectional multicenter study was conducted between January 2018 and August 2019 in 1000 healthy children under two years of age. We use standard microbiological methods to determinate S. pneumoniae from nasopharyngeal swab, Kirby Bauer and minimum inhibitory concentration methods to determinate antimicrobial susceptibility and whole genomic sequencing to determinate pneumococcal serotypes. RESULTS: The pneumococcal carriage rate was 20.8 % vs. 31.1 % in pre-PCV7 (p < 0.001). The most frequent serotypes were 15C, 19A and 6C (12.4 %, 10.9 % and 10.9 % respectively). The carriage of PCV13 serotypes after PCV13 introduction decreased from 59.1 % (before PCV7 introduction) to 18.7 % (p < 0.001). Penicillin resistance was 75.5 %, TMP/SMX 75.5 % and azithromycin 50.0 %, using disk diffusion. Penicillin resistance rates using MIC breakpoint for meningitis (MIC ≥ 0.12) increased from 60.4 % to 74.5 % (p = 0.001). CONCLUSION: The introduction of PCV13 in the immunization program in Peru has decreased the pneumococcal nasopharyngeal carriage and the frequency of PCV13 serotypes; however, there has been an increase in non-PCV13 serotypes and antimicrobial resistance.

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) Prepared by Microwave and Ultrasound-Assisted Synthesis: Promising Green Strategies for the Nanoworld.

Many pharmaceutically active molecules are highly lipophilic, which renders their administration and adsorption in patients extremely challenging. Among the countless strategies to overcome this problem, synthetic nanocarriers have demonstrated superb efficiency as drug delivery systems, since encapsulation can effectively prevent a molecules' degradation, thus ensuring increased biodistribution. However, metallic and polymeric nanoparticles have been frequently associated with possible cytotoxic side effects. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which are prepared with physiologically inert lipids, therefore emerged as an ideal strategy to bypass toxicities issues and avoid the use of organic solvents in their formulations. Different approaches to preparation, using only moderate amounts of external energy to facilitate a homogeneous formation, have been proposed. Greener synthesis strategies have the potential to provide faster reactions, more efficient nucleation, better particle size distribution, lower polydispersities, and furnish products with higher solubility. Particularly microwave-assisted synthesis (MAS) and ultrasound-assisted synthesis (UAS) have been utilized in the manufacturing of nanocarrier systems. This narrative review addresses the chemical aspects of those synthesis strategies and their positive influence on the characteristics of SLNs and NLCs. Furthermore, we discuss the limitations and future challenges for the manufacturing processes of both types of nanoparticles.