Topological Fano-resonance with type-II and type-III corner states.

Topological corner states have been used to develop topologically robust Fano-resonant systems immune to structural perturbations while preserving the ultra-sensitive profiles under external factors. In this work, we have extended the possibility of obtaining Fano-resonant systems by introducing type-II and type-III corner states with a large modal surface to this class of resonance. Through photonic lattices with low symmetry, such as C2, it is easy to obtain type-II and type-III corner states due to the tailoring of long-range interactions. Subsequently, one can combine topological cavities of type-II and type-III corner modes with topological waveguides obtained from a first-order topological insulating phase. Our results may pave the way to generate devices suitable for creating non-classical light applicable in quantum computing and ultra-sensitive sensors employing large-area topological states.

NOTCH4 potentiates the IL-13 induced genetic program in M2 alternative macrophages through the AP1 and IRF4-JMJD3 axis.

IL-13 signaling polarizes macrophages to an M2 alternatively activated phenotype, which regulates tissue repair and anti-inflammatory responses. However, an excessive activation of this pathway leads to severe pathologies, such as allergic airway inflammation and asthma. In this work, we identified NOTCH4 receptor as an important modulator of M2 macrophage activation. We show that the expression of NOTCH4 is induced by IL-13, mediated by Janus kinases and AP1 activity, probably mediated by the IL-13Rα1 and IL-13Rα2 signaling pathway. Furthermore, we demonstrate an important role for NOTCH4 signaling in the IL-13 induced gene expression program in macrophages, including various genes that contribute to pathogenesis of the airways in asthma, such as ARG1, YM1, CCL24, IL-10, or CD-163. We also demonstrate that NOTCH4 signaling modulates IL-13-induced gene expression by increasing IRF4 activity, mediated, at least in part, by the expression of the histone H3K27me3 demethylase JMJD3, and by increasing AP1-dependent transcription. In summary, our results provide evidence for an important role of NOTCH4 signaling in alternative activation of macrophages by IL-13 and suggest that NOTCH4 may contribute to the increased severity of lesions in M2 inflammatory responses, such as allergic asthma, which points to NOTCH4 as a potential new target for the treatment of these pathologies.

Expression and purification of an NP-hoc fusion protein: Utilizing influenza a nucleoprotein and phage T4 hoc protein.

Influenza poses a substantial health risk, with infants and the elderly being particularly susceptible to its grave impacts. The primary challenge lies in its rapid genetic evolution, leading to the emergence of new Influenza A strains annually. These changes involve punctual mutations predominantly affecting the two main glycoproteins: Hemagglutinin (HA) and Neuraminidase (NA). Our existing vaccines target these proteins, providing short-term protection, but fall short when unexpected pandemics strike. Delving deeper into Influenza's genetic makeup, we spotlight the nucleoprotein (NP) - a key player in the transcription, replication, and packaging of RNA. An intriguing characteristic of the NP is that it is highly conserved across all Influenza A variants, potentially paving the way for a more versatile and broadly protective vaccine. We designed and synthesized a novel NP-Hoc fusion protein combining Influenza A nucleoprotein and T4 phage Hoc, cloned using Gibson assembly in E. coli, and purified via ion affinity chromatography. Simultaneously, we explore the T4 coat protein Hoc, typically regarded as inconsequential in controlled viral replication. Yet, it possesses a unique ability: it can link with another protein, showcasing it on the T4 phage coat. Fusing these concepts, our study designs, expresses, and purifies a novel fusion protein named NP-Hoc. We propose this protein as the basis for a new generation of vaccines, engineered to guard broadly against Influenza A. The excitement lies not just in the immediate application, but the promise this holds for future pandemic resilience, with NP-Hoc marking a significant leap in adaptive, broad-spectrum influenza prevention.

Use of Darvadstrocel (Allogenic Stem Cell Therapy) for Crohn's Fistulas in Real Clinical Practice: The National Project to Implement Mesenchymal Stem Cell for the Treatment of Perianal Crohn's Fistula (the PRIME Study).

BACKGROUND: Perianal fistulas may affect 15% to 50% of patients with Crohn's disease. Treatment is complex, requiring a multidisciplinary approach. Darvadstrocel (allogenic mesenchymal cells obtained from lipoaspirates) was approved in 2018 by the European and Spanish Agencies of Medicines and Medical Products as a treatment for fistulas in Crohn's disease. Recent guidelines from the European Crohn's and Colitis Organisation and Spanish Working Group on Crohn's Disease and Ulcerative Colitis state that darvadstrocel is effective with a favorable safety profile and a strong level of evidence (n = 2). OBJECTIVE: Presenting real-world effectiveness data for darvadstrocel in a Spanish population. DESIGN: Observational retrospective cohort study with prospective data gathering. SETTINGS: The study was conducted at 14 institutions in Spain. PATIENTS: From November 2019 to April 2022, all patients (n = 73) treated with darvadstrocel in these institutions were included, fulfilling the following criteria: 1) complex fistula/s in a patient with Crohn's disease; 2) failure of conventional and antitumor necrosis factor treatment; and 3) the absence of collections of >2 cm confirmed by pelvic MRI at the time of surgery. INTERVENTIONS: Darvadstrocel treatment. MAIN OUTCOME MEASURES: Clinical response (closure of 50% or more of external openings), complete clinical closure (100% of external openings), and radiological closure (no fluid collection >2 cm, edema, or inflammation) evaluated 6 months after treatment. RESULTS: Clinical response was observed in 63 patients (86.3%), complete clinical closure in 50 patients (68.5%), and radiological closure in 45 patients (69.2%). Combined clinical and radiological response was observed in 41 patients (63.1%). Not all clinically healed patients had radiological closure, and vice versa. No serious adverse events were reported. LIMITATIONS: Retrospective nature of the study. CONCLUSIONS: Study results were consistent with those reported in previous clinical trials, real-world efficacy findings from the INSPIRE study (assessing darvadstrocel effectiveness in Europe, Israel, Switzerland, United Kingdom, and Japan), and previously published literature. Darvadstrocel was effective and demonstrated a favorable safety profile when used in normal clinical practice for the treatment of fistulas in Crohn's disease. See Video Abstract . USO DE DARVADSTROCEL TERAPIA CON CLULAS MADRE ALOGNICAS PARA FSTULA EN ENFERMEDAD DE CROHN EN LA PRCTICA CLNICA REAL EL PROYECTO NACIONAL PARA IMPLEMENTAR DE CLULAS MADRE MESENQUIMALES PARA EL TRATAMIENTO DE LA FSTULA DE CROHN PERIANAL EL ESTUDIO PRIME: ANTECEDENTES:Las fístulas perianales pueden afectar entre el 15 y el 50% de los pacientes con enfermedad de Crohn. El tratamiento es complejo y requiere un enfoque multidisciplinario. El darvadstrocel (células mesenquimales alogénicas obtenidas a partir de lipoaspirados) fue aprobado en 2018 por las Agencias Europea y Española de Medicamentos y Productos Sanitarios como tratamiento de las fístulas en la EC. Las recientes directrices de la Organización Europea de Crohn y Colitis y del Grupo de Trabajo Español sobre la Enfermedad de Crohn y Colitis Ulcerosa afirman que darvadstrocel es eficaz con un perfil de seguridad favorable y un sólido nivel de evidencia (2).OBJETIVO:Presentar datos de eficacia real de darvadstrocel en población española.DISEÑO:Estudio de cohorte retrospectivo observacional con recopilación prospectiva de datos.ESCENARIO:14 instituciones.PACIENTES:Desde noviembre de 2019 hasta abril de 2022, se incluyeron todos los pacientes (73) tratados con darvadstrocel en estas instituciones, que cumplieron los siguientes criterios: 1) fístula/s compleja/s en un paciente con enfermedad de Crohn; 2) fracaso del tratamiento convencional y anti factor de necrosis tumoral; 3) ausencia de colecciones > 2 cm confirmada por resonancia magnética pélvica en el momento de la cirugía.INTERVENCIONES:Tratamiento con Darvadstrocel.PRINCIPALES MEDIDAS DE RESULTADO:Respuesta clínica (cierre de ≥50% de las aberturas externas), cierre clínico completo (100% de las aberturas externas) y cierre radiológico (sin acumulación de líquido >2 cm, sin edema ni inflamación) evaluados 6 meses después del tratamiento.RESULTADOS:Se observó respuesta clínica en 63 pacientes (86.3%), cierre clínico completo en 50 pacientes (68.5%) y cierre radiológico en 45 pacientes (69.2%). Se observó respuesta clínica y radiológica combinada en 41 pacientes (63.1%). No todos los pacientes clínicamente curados tuvieron cierre radiológico y viceversa. No hubo eventos adversos graves reportados.LIMITACIONES:Estudio retrospectivoCONCLUSIONES:Los resultados del estudio fueron consistentes con los informados en ensayos clínicos anteriores, los hallazgos de eficacia en el mundo real del estudio INSPIRE (que evalúa la efectividad de darvadstrocel en Europa, Israel, Suiza, el Reino Unido y Japón) y la literatura publicada anteriormente. Darvadstrocel fue eficaz y demostró un perfil de seguridad favorable cuando se utiliza en la práctica clínica habitual para el tratamiento de fístulas en la enfermedad de Crohn. (Traducción-Dr. Jorge Silva Velazco ).

Molecular detection of Histoplasma capsulatum in organ samples from bats randomly captured in urban areas of Araraquara, São Paulo state, Brazil.

The mycosis histoplasmosis is also considered a zoonosis that affects humans and other mammalian species worldwide. Among the wild mammals predisposed to be infected with the etiologic agent of histoplasmosis, bats are relevant because they are reservoir of Histoplasma species, and they play a fundamental role in maintaining and spreading fungal propagules in the environments since the infective mycelial phase of Histoplasma grows in their accumulated guano. In this study, we detected the fungal presence in organ samples of bats randomly captured in urban areas of Araraquara City, São Paulo, Brazil. Fungal detection was performed using a nested polymerase chain reaction to amplify a molecular marker (Hcp100) unique to H. capsulatum, which revealed the pathogen presence in organ samples from 15 out of 37 captured bats, indicating 40.5% of infection. Out of 22 Hcp100-amplicons generated, 41% corresponded to lung and trachea samples and 59% to spleen, liver, and kidney samples. Data from these last three organs suggest that bats develop disseminated infections. Considering that infected bats create environments with a high risk of infection, it is important to register the percentage of infected bats living in urban areas to avoid risks of infection to humans, domestic animals, and wildlife.

ZnO Decorated Graphene-Based NFC Tag for Personal NO2 Exposure Monitoring during a Workday.

This paper presents the integration of a sensing layer over interdigitated electrodes and an electronic circuit on the same flexible printed circuit board. This integration provides an effective technique to use this design as a wearable gas measuring system in a target application, exhibiting high performance, low power consumption, and being lightweight for on-site monitoring. The wearable system proves the concept of using an NFC tag combined with a chemoresistive gas sensor as a cumulative gas sensor, having the possibility of holding the data for a working day, and completely capturing the exposure of a person to NO2 concentrations. Three different types of sensors were tested, depositing the sensing layers on gold electrodes over Kapton substrate: bare graphene, graphene decorated with 5 wt.% zinc oxide nanoflowers, or nanopillars. The deposited layers were characterized using FESEM, EDX, XRD, and Raman spectroscopy to determine their crystalline structure, morphological and chemical compositions. The gas sensing performance of the sensors was analyzed against NO2 (dry and humid conditions) and other interfering species (dry conditions) to check their sensitivity and selectivity. The resultant-built wearable NFC tag system accumulates the data in a non-volatile memory every minute and has an average low power consumption of 24.9 µW in dynamic operation. Also, it can be easily attached to a work vest.

Cilastatin as a Potential Anti-Inflammatory and Neuroprotective Treatment in the Management of Glaucoma.

Glaucoma is a neurodegenerative disease that causes blindness. In this study, we aimed to evaluate the protective role of cilastatin (CIL), generally used in the treatment of nephropathologies associated with inflammation, in an experimental mouse model based on unilateral (left) laser-induced ocular hypertension (OHT). Male Swiss mice were administered CIL daily (300 mg/kg, i.p.) two days before OHT surgery until sacrifice 3 or 7 days later. Intraocular Pressure (IOP), as well as retinal ganglion cell (RGC) survival, was registered, and the inflammatory responses of macroglial and microglial cells were studied via immunohistochemical techniques. Results from OHT eyes were compared to normotensive contralateral (CONTRA) and naïve control eyes considering nine retinal areas and all retinal layers. OHT successfully increased IOP values in OHT eyes but not in CONTRA eyes; CIL did not affect IOP values. Surgery induced a higher loss of RGCs in OHT eyes than in CONTRA eyes, while CIL attenuated this loss. Similarly, surgery increased macroglial and microglial activation in OHT eyes and to a lesser extent in CONTRA eyes; CIL prevented both macroglial and microglial activation in OHT and CONTRA eyes. Therefore, CIL arises as a potential effective strategy to reduce OHT-associated damage in the retina of experimental mice.

Light-Responsive and Dual-Targeting Liposomes: From Mechanisms to Targeting Strategies.

In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.

Use of Novel Homochiral Thioureas Camphor Derived as Asymmetric Organocatalysts in the Stereoselective Formation of Glycosidic Bonds.

We synthesized six new camphor-derived homochiral thioureas 1-6, from commercially available (1R)-(-)-camphorquinone. These new compounds 1-6 were evaluated as asymmetric organocatalysts in the stereoselective formation of glycosidic bonds, with 2,3,4,6-tetra-O-benzyl-D-glucopyranosyl and 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates as donors, and several alcohols as glycosyl acceptors, such as methanol, ethanol, 1-propanol, 1-butanol, 1-octanol, iso-propanol, tert-butanol, cyclohexanol, phenol, 1-naphtol, and 2-naphtol. Optimization of the asymmetric glycosylation reaction was achieved by modifying reaction conditions such as solvent, additive, loading of catalyst, temperature, and time of reaction. The best result was obtained with 2,3,4,6-tetra-O-benzyl-D-galactopyranosyl trichloroacetimidates, using 15 mol% of organocatalyst 1, in the presence of 2 equiv of MeOH in solvent-free conditions at room temperature for 1.5 h, affording the glycosidic compound in a 99% yield and 1:73 α:ß stereoselectivity; under the same reaction conditions, without using a catalyst, the obtained stereoselectivity was 1:35 α:ß. Computational calculations prior to the formation of the products were modeled, using density functional theory, M06-2X/6-31G(d,p) and M06-2X/6-311++G(2d,2p) methods. We observed that the preference for ß glycoside formation, through a stereoselective inverted substitution, relies on steric effects and the formation of hydrogen bonds between thiourea 1 and methanol in the complex formed.

Probiotics: insights and new opportunities for Clostridioides difficile intervention.

Clostridioides difficile infection (CDI) is a life-threatening disease caused by the Gram-positive, opportunistic intestinal pathogen C. difficile. Despite the availability of antimicrobial drugs to treat CDI, such as vancomycin, metronidazole, and fidaxomicin, recurrence of infection remains a significant clinical challenge. The use of live commensal microorganisms, or probiotics, is one of the most investigated non-antibiotic therapeutic options to balance gastrointestinal (GI) microbiota and subsequently tackle dysbiosis. In this review, we will discuss major commensal probiotic strains that have the potential to prevent and/or treat CDI and its recurrence, reassess the efficacy of probiotics supplementation as a CDI intervention, delve into lessons learned from probiotic modulation of the immune system, explore avenues like genome-scale metabolic network reconstructions, genome sequencing, and multi-omics to identify novel strains and understand their functionality, and discuss the current regulatory framework, challenges, and future directions.

Mesenchymal stem cells attenuate the proinflammatory cytokine pattern in a guinea pig model of chronic cigarette smoke exposure.

AIMS: Cigarette smoke often induces pulmonary and systemic inflammation. In animal models, mesenchymal stem cells (MSC) tend to ameliorate these effects. We aimed to explore the local and systemic expression of cytokines in guinea pigs chronically exposed to cigarette smoke, and their modifications by MSC. MAIN METHODS: Concentrations of IL-1ß, IL-6, IL-8, IL-12, TNF-α, INF-É£, TSG-6, MMP-9, TIMP-1, and/or TIMP-2 in serum and bronchoalveolar lavage (BALF) from animals exposed to tobacco smoke (20 cigarettes/day, 5 days/week for 10 weeks) were determined, and mRNA expression of some of them was measured in lung tissue. Intratracheal instillation of allogeneic bone marrow MSC (5x106 cells in 1 ml) was done at week 2. KEY FINDINGS: After cigarette smoke, IL-6 and IFN-γ increased in serum and BALF, while IL-1ß and IL-12 decreased in serum, and TSG-6 and TIMP-2 increased in BALF. IL-1ß had a paradoxical increase in BALF. MSC had an almost null effect in unexposed animals. The intratracheal administration of MSC in guinea pigs exposed to cigarette smoke was associated with a statistically significant decrease of IL-12 and TSG-6 in serum, as well as a decrease of IL-1ß and IFN-γ and an increase in TIMP-1 in BALF. Concerning mRNA expression in lung tissue, cigarette smoke did not modify the relative amount of the studied transcripts, but even so, MSC decreased the IL-12 mRNA and increased the TIMP-1 mRNA. SIGNIFICANCE: A single intratracheal instillation of MSC reduces the pulmonary and systemic proinflammatory pattern induced by chronic exposure to cigarette smoke in guinea pigs. TRIAL REGISTRATION: Not applicable.

The future of cassava in the era of biotechnology in Southern Africa.

Cassava (Manihot esculenta) is a major staple food and the world's fourth source of calories. Biotechnological contributions to enhancing this crop, its advances, and present issues must be assessed regularly. Functional genomics, genomic-assisted breeding, molecular tools, and genome editing technologies, among other biotechnological approaches, have helped improve the potential of economically important crops like cassava by addressing some of its significant constraints, such as nutrient deficiency, toxicity, poor starch quality, disease susceptibility, low yield capacity, and postharvest deterioration. However, the development, improvement, and subsequent acceptance of the improved cultivars have been challenging and have required holistic approaches to solving them. This article provides an update of trends and gaps in cassava biotechnology, reviewing the relevant strategies used to improve cassava crops and highlighting the potential risk and acceptability of improved cultivars in Southern Africa.

Use of telehealth for psychosocial oncology: A mixed methods study about barriers to and opportunities with Latino patients from Latin America, Spain, and the United States.

OBJECTIVES: Telehealth for mental healthcare expanded rapidly with the COVID-19 pandemic's onset; however, global access disparities emerged. Telehealth challenges and opportunities for Latino cancer patients from different geographical regions must be explored. METHODS: A cross-sectional online survey (March-July 2021) of mental health providers, serving Latino cancer patients in Latin America, United States, and Spain, contained close-ended questions related to the use of telehealth during the pandemic and open-ended questions on recommending/not recommending telehealth. RESULTS: In a sample of 148 providers from 21 countries, 60.5% reported that at least some of their patients had difficulties with Internet speed and connectivity and lacked knowledge about using electronic devices (43.2%) or the Internet (45.4%). Lacking privacy at home (66.0%) and childcare (26.0%) were reported patient challenges. Internet connectivity or speed were issues for providers (43.2%) themselves. Improving patient reach was a reported telehealth benefit (64.2%). Geographical access (43.2%) and physical limitations (35.8%) were considerations in offering telehealth. Considerations for not recommending telehealth were patient age (24.3%) and lacking technological knowledge (29.1%). CONCLUSIONS: Telehealth for mental healthcare may improve patient access issues caused by geographical and transportation conditions and patient functionality. Findings provide insight into telehealth benefits and challenges in Latino patient populations. Future studies should examine patient access and use by region.

Design of a nanobiosystem with remote photothermal gene silencing in Chlamydomonas reinhardtii to increase lipid accumulation and production.

Research development in the precise control of gene expression in plant cells is an emerging necessity that would lead to the elucidation of gene function in these biological systems. Conventional gene-interfering techniques, such as micro-RNA and short interfering RNA, have limitations in their ability to downregulate gene expression in plants within short time periods. However, nanotechnology provides a promising new avenue with new tools to overcome these challenges. Here, we show that functionalized gold nanoparticles, decorated with sense and antisense oligonucleotides (FANSAO), can serve as a remote-control optical switch for gene interference in photosynthetic plant cells. We demonstrate the potential of employing LEDs as optimal light sources to photothermally dehybridize the oligonucleotides on the surface of metallic nanostructures, consequently inducing regulation of gene expression in plant cells. We show the efficiency of metallic nanoparticles in absorbing light from an LED source and converting it to thermal energy, resulting in a local temperature increase on the surface of the gold nanoparticles. The antisense oligonucleotides are then released due to the opto-thermal heating of the nanobiosystem composed of the metallic nanoparticles and the sense-antisense oligonucleotides. By applying this approach, we silenced the Carnitine Acyl Carnitine Translocase genes at 90.7%, resulting in the accumulation of lipid bodies in microalgae cells. These results exhibit the feasibility of using functionalized gold nanoparticles with sense and antisense oligonucleotides to enhance nucleic acid delivery efficiency and, most importantly, allow for temporal control of gene silencing in plant cells. These nanobiosystems have broad applications in the development and biosynthesis of biofuels, pharmaceuticals, and specialized chemicals.

Home-based prehabilitation improves physical conditions measured by ergospirometry and 6MWT in colorectal cancer patients: a randomized controlled pilot study.

PURPOSE/BACKGROUND: Prehabilitation aims to improve physical condition in the preoperative period and, therefore, decrease the loss of cardiopulmonary capacity postoperatively, with the aim of reducing complications and promoting an early recovery. This study aims to evaluate the impact of home-based prehabilitation on the physical condition of patients treated surgically for colorectal cancer. METHODS: A prospective and randomized clinical study was conducted on 60 patients during two periods from October 2018 to February 2019 and from September 2019 to September 2020, in a single university hospital. Patients were randomized into two study groups (30 per group): prehabilitation vs. standard care. Changes in physical condition, measured at diagnosis, the day before surgery, and at 6-8 weeks after surgery using the cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) were evaluated. RESULTS: Prehabilitation reduced postoperative complications (17.4% vs. 33.3%, p = 0.22) and hospital stay (5.74 vs. 6.67 days, p = 0.30). 6MWT showed a significant improvement in the prehabilitation group (+78.9 m). Six weeks after surgery, prehabilitation showed a significant improvement in the 6MWT (+68.9 m vs. -27.2 m, p = 0.01). Significant differences were also observed in the ergospirometry between the diagnosis and postoperative study (+0.79 METs vs. -0.84 METs, p = 0.001). A strong correlation was observed between CPET and 6MWT (0.767 (p < 0.001)). CONCLUSION: Home prehabilitation achieved lower overall postoperative complications than standard care and reached significant improvements in 6MWT and CET. A strong correlation was observed between CET and 6MWT, which allows validation of 6MWT as a valid and reliable measure of functional exercise capacity in colorectal patients when other, more specific and expensive tests are not available. TRIAL REGISTRATION: Registered in ClinicalTrials.gov in August 2018 with registration number https://clinicaltrials.gov/study/NCT03618329?cond=Prehabilitation%20cancer&term=arroyo&distance=50&rank=1  (NCT03618329). Initial results published in Supportive Care in Cancer: Effect of home-based prehabilitation in an enhanced recovery after surgery program for patients undergoing colorectal cancer surgery during the COVID-19 pandemic. DOI: https://doi.org/10.1007/s00520-021-06343-1 .

Logistical, technical, and radiation safety aspects of establishing a radiopharmaceutical therapy program: A case in Lutetium-177 prostate-specific membrane antigen (PSMA) therapy.

Prostate-specific membrane antigen (PSMA) is a cell surface protein highly expressed in nearly all prostate cancers, with restricted expression in some normal tissues. The differential expression of PSMA from tumor to non-tumor tissue has resulted in the investigation of numerous targeting strategies for therapy of patients with metastatic prostate cancer. In March of 2022, the FDA granted approval for the use of lutetium-177 PSMA-617 (Lu-177-PSMA-617) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. Therefore, the use of Lu-177-PSMA-617 is expected to increase and become more widespread. Herein, we describe logistical, technical, and radiation safety considerations for implementing a radiopharmaceutical therapy program, with particular focus on the development of operating procedures for therapeutic administrations. Major steps for a center in the U.S. to implement a new radiopharmaceutical therapy (RPT) program are listed below, and then demonstrated in greater detail via examples for Lu-177-PSMA-617 therapy.

[Comparative analysis of the accreditation of medical facilities in Canada, Chile, the Autonomous Community of Andalusia, Denmark, and MexicoAnálise comparativa da acreditação de estabelecimentos de saúde no Canadá, Chile, Comunidade Autônoma da Andaluzia, Dinamarca e México]. / Análisis comparativo de la acreditación de unidades médicas en Canadá, Chile, la Comunidad Autónoma de Andalucía, Dinamarca y México.

Objective: To compare and contrast the characteristics of the accreditation process for health care facilities in Canada, Chile, the Autonomous Community of Andalusia (Spain), Denmark, and Mexico, in order to identify shared characteristics, differences, and lessons learned that may be useful for other countries and regions. Methods: An observational, analytical, retrospective study using open-access secondary sources on the accreditation and certification of health care facilities in 2019-2021 in these countries and regions. The general characteristics of the accreditation processes are described and comments are made on key aspects of the design of these programs. Additionally, analytical categories were created for degree of implementation and level of complexity, and the positive and negative results reported are summarized. Results: The operational components of the accreditation processes are country-specific, although they share similarities. The Canadian program is the only one that involves some form of responsive evaluation. There is a wide range in the percentage of establishments accredited from country to country (from 1% in Mexico to 34.7% in Denmark). Notable lessons learned include the complexity of application in a mixed public-private system (Chile), the risk of excessive bureaucratization (Denmark), and the need for clear incentives (Mexico). Conclusions: The accreditation programs operate in a unique way in each country and region, achieve varying degrees of implementation, and have an assortment of problems, from which lessons can be learned. Elements that hinder their implementation should be considered and adjustments made for the health systems of each country and region.

Objetivo: Comparar as características do processo de acreditação de estabelecimentos de saúde no Canadá, Chile, Comunidade Autônoma da Andaluzia, Dinamarca e México, a fim de identificar elementos comuns e diferenças, bem como lições aprendidas que podem ser úteis para outros países e regiões. Métodos: Estudo observacional, analítico e retrospectivo usando fontes secundárias de livre acesso sobre acreditação e certificação de estabelecimentos de saúde durante o período 2019-2021 nos países e regiões supracitados. As características gerais do processo de acreditação e suas respostas a pontos-chave no delineamento de tais programas foram descritas. Além disso, foram geradas categorias de análise para o andamento de sua implantação e seu grau de complexidade, e os desfechos favoráveis e desfavoráveis relatados foram resumidos. Resultados: Os componentes operacionais do processo de acreditação são peculiares a cada país, embora compartilhem certas semelhanças. O programa canadense é o único que contempla algum tipo de avaliação responsiva. Houve grande variação entre países no percentual de estabelecimentos acreditados (de 1% no México a 34,7% na Dinamarca). Entre as lições aprendidas, destacam-se a complexidade da aplicação do sistema misto público-privado (Chile), o risco de burocratização excessiva (Dinamarca) e a necessidade de incentivos claros (México). Conclusões: Os programas de acreditação operam de forma peculiar em cada país ou região, têm diferentes escopos e também apresentam diversos problemas a partir dos quais podemos aprender. É preciso considerar os elementos que dificultam a implementação e realizar as adequações necessárias para os sistemas de saúde de cada país ou região.

Microbiology and Biochemistry of Pesticides Biodegradation.

Pesticides are chemicals used in agriculture, forestry, and, to some extent, public health. As effective as they can be, due to the limited biodegradability and toxicity of some of them, they can also have negative environmental and health impacts. Pesticide biodegradation is important because it can help mitigate the negative effects of pesticides. Many types of microorganisms, including bacteria, fungi, and algae, can degrade pesticides; microorganisms are able to bioremediate pesticides using diverse metabolic pathways where enzymatic degradation plays a crucial role in achieving chemical transformation of the pesticides. The growing concern about the environmental and health impacts of pesticides is pushing the industry of these products to develop more sustainable alternatives, such as high biodegradable chemicals. The degradative properties of microorganisms could be fully exploited using the advances in genetic engineering and biotechnology, paving the way for more effective bioremediation strategies, new technologies, and novel applications. The purpose of the current review is to discuss the microorganisms that have demonstrated their capacity to degrade pesticides and those categorized by the World Health Organization as important for the impact they may have on human health. A comprehensive list of microorganisms is presented, and some metabolic pathways and enzymes for pesticide degradation and the genetics behind this process are discussed. Due to the high number of microorganisms known to be capable of degrading pesticides and the low number of metabolic pathways that are fully described for this purpose, more research must be conducted in this field, and more enzymes and genes are yet to be discovered with the possibility of finding more efficient metabolic pathways for pesticide biodegradation.

CBD Inhibits In Vivo Development of Human Breast Cancer Tumors.

Inflammation is a critical component of cancer development. Previously, we showed in vitro that IL-1ß treatment of non-invasive human breast cancer MCF-7 cells promoted their transition to a malignant phenotype (6D cells). This epithelial-mesenchymal transition was reverted by exposure to cannabidiol (CBD). We show in a murine model that subcutaneous inoculation of 6D cells induced formation and development of tumors, the cells of which keep traits of malignancy. These processes were interrupted by administration of CBD under two schemes: therapeutic and prophylactic. In the therapeutic scheme, 6D cells inoculated mice developed tumors that reached a mean volume of 540 mm3 at 45 days, while 50% of CBD-treated mice showed gradual resorption of tumors. In the prophylactic scheme, mice were pre-treated for 15 days with CBD before cells inoculation. The tumors formed remained small and were eliminated under continuous CBD treatment in 66% of the animals. Histological and molecular characterization of tumors, from both schemes, revealed that CBD-treated cells decreased the expression of malignancy markers and show traits related with apoptosis. These results confirm that in vivo CBD blocks development of breast cancer tumors formed by cells induced to malignancy by IL-1ß, endorsing its therapeutic potential for cancer treatment.

The Role of Citicoline and Coenzyme Q10 in Retinal Pathology.

Ocular neurodegenerative diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration are common retinal diseases responsible for most of the blindness causes in the working-age and elderly populations in developed countries. Many of the current treatments used in these pathologies fail to stop or slow the progression of the disease. Therefore, other types of treatments with neuroprotective characteristics may be necessary to allow a more satisfactory management of the disease. Citicoline and coenzyme Q10 are molecules that have neuroprotective, antioxidant, and anti-inflammatory properties, and their use could have a beneficial effect in ocular neurodegenerative pathologies. This review provides a compilation, mainly from the last 10 years, of the main studies that have been published on the use of these drugs in these neurodegenerative diseases of the retina, analyzing the usefulness of these drugs in these pathologies.