Synthesis and Anti-Trypanosoma cruzi Activity of 3-Cyanopyridine Derivatives.

Chagas disease (CD) is a parasitic neglected tropical disease (NTD) caused by the protozoan Trypanosoma cruzi that affects 6 million people worldwide, often resulting in financial burden, morbidity, and mortality in endemic regions. Given a lack of highly efficient and safe treatments, new, affordable, and fit-for-purpose drugs for CD are urgently needed. In this work, we present a hit-to-lead campaign for novel cyanopyridine analogues as antichagasic agents. In a phenotypic screening against intracellular T. cruzi, hits 1 and 2 were identified and displayed promising potency combined with balanced physicochemical properties. As part of the Lead Optimization Latin America consortium, a set of 40 compounds was designed, synthesized, and tested against T. cruzi intracellular amastigotes and relevant human cell lines. The structural modifications were focused on three positions: cyanopyridine core, linker, and right-hand side. The ADME properties of selected compounds, lipophilicity, kinetic solubility, permeability, and liver microsomal stability, were evaluated. Compounds 1-9 displayed good potency (EC50T. cruzi amastigote <1 µM), and most compounds did not present significant cytotoxicity (CC50 MRC-5 = 32-64 µM). Despite the good balance between potency and selectivity, the antiparasitic activity of the series appeared to be driven by lipophilicity, making the progression of the series unfeasible due to poor ADME properties and potential promiscuity issues.

U.S. cereal rye winter cover crop growth database.

Winter cover crop performance metrics (i.e., vegetative biomass quantity and quality) affect ecosystem services provisions, but they vary widely due to differences in agronomic practices, soil properties, and climate. Cereal rye (Secale cereale) is the most common winter cover crop in the United States due to its winter hardiness, low seed cost, and high biomass production. We compiled data on cereal rye winter cover crop performance metrics, agronomic practices, and soil properties across the eastern half of the United States. The dataset includes a total of 5,695 cereal rye biomass observations across 208 site-years between 2001-2022 and encompasses a wide range of agronomic, soils, and climate conditions. Cereal rye biomass values had a mean of 3,428 kg ha-1, a median of 2,458 kg ha-1, and a standard deviation of 3,163 kg ha-1. The data can be used for empirical analyses, to calibrate, validate, and evaluate process-based models, and to develop decision support tools for management and policy decisions.

Diagnostic accuracy of MRI, CT, and [18F]FDG-PET-CT in detecting lymph node metastases in clinically early-stage cervical cancer - a nationwide Dutch cohort study.

OBJECTIVES: Imaging is increasingly used to assess lymph node involvement in clinically early-stage cervical cancer. This retrospective study aimed to evaluate the diagnostic accuracy of MRI, CT, and [18F]FDG-PET-CT. METHODS: Women with International Federation of Gynaecology and Obstetrics (FIGO) 2009 stage IA2-IIA cervical cancer and pretreatment imaging between 2009 and 2017 were selected from the Netherlands Cancer Registry. Patient-based and region-based (i.e. pelvic and common iliac) nodal status was extracted from radiology reports. Pathology results were considered the reference standard for calculating accuracy indices. Multiple imputation was used for missing pathology to limit verification bias risk. RESULTS: Nodal assessment was performed in 1676 patients with MRI, 926 with CT, and 379 with [18F]FDG-PET-CT, with suspicious nodes detected in 17%, 16%, and 48%, respectively. [18F]FDG-PET-CT was used to confirm MRI/CT results in 95% of patients. Pathology results were imputed for 30% of patients. [18F]FDG-PET-CT outperformed MRI and CT in detecting patient-based nodal metastases with sensitivities of 80%, 48%, and 40%, and AUCs of 0.814, 0.706, and 0.667, respectively, but not in specificity: 79%, 92%, and 92%. Region-based analyses showed similar indices in the pelvic region, but worse performance in the common iliac region with AUCs of 0.575, 0.554, and 0.517, respectively. CONCLUSIONS: [18F]FDG-PET-CT outperformed MRI and CT in detecting nodal metastases, which may be related to its use as a verification modality. However, MRI and CT had the highest specificity. As MRI is generally performed routinely to assess local and regional spread of cervical cancer, [18F]FDG-PET-CT can be used to confirm suspicious nodes. CRITICAL RELEVANCE STATEMENT: Accurate assessment of the nodal status in clinically early-stage cervical cancer is essential for tumour staging, treatment decision making and prognosis. KEY POINTS: • The accuracy of MRI, CT or [18F]FDG-PET-CT for nodal staging in early cervical cancer is a subject of discussion. • Overall, [18F]FDG-PET-CT outperformed MRI, followed by CT, when used as a verification modality. • Staging with MRI and the addition of [18F]FDG-PET-CT to verify high-risk cases seems to be a good approach.

PROTAC for agriculture: learning from human medicine to generate new biotechnological weed control solutions.

Weed control has relied on the use of organic and inorganic molecules that interfere with druggable targets, especially enzymes, for almost a century. This approach, although effective, has resulted in multiple cases of herbicide resistance. Furthermore, the rate of discovery of new druggable targets that are selective and with favorable environmental profiles has slowed down, highlighting the need for innovative control tools. The arrival of the biotechnology and genomics era gave hope to many that all sorts of new control tools would be developed. However, the reality is that most efforts have been limited to the development of transgenic crops with resistance to a few existing herbicides, which in fact is just another form of selectivity. Proteolysis-targeting chimera (PROTAC) is a new technology developed to treat human diseases but that has potential for multiple applications in agriculture. This technology uses a small bait molecule linked to an E3 ligand. The 3-dimensional structure of the bait favors physical interaction with a binding site in the target protein in a manner that allows E3 recruitment, ubiquitination and then proteasome-mediated degradation. This system makes it possible to circumvent the need to find druggable targets because it can degrade structural proteins, transporters, transcription factors, and enzymes without the need to interact with the active site. PROTAC can help control herbicide-resistant weeds as well as expand the number of biochemical targets that can be used for weed control. In the present article, we provide an overview of how PROTAC works and describe the possible applications for weed control as well as the challenges that this technology might face during development and implementation for field uses. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

The impact of burial depth on Centaurea diluta emergence and modelling of its growth using a nonlinear regression and artificial neural network.

BACKGROUND: Centaurea diluta Aiton (North African knapweed) is a major weed concern in Spain as a result of the limited herbicides capable of controlling it, and the limited knowledge of its biology hinders the development of integrated weed management strategies. RESULTS: The current study presents results from two experiments that aimed to: (i) determine the effect of seed burial on seedling emergence; and (ii) model its phenology progression using sigmoidal (SRM) and artificial neural network models (ANN) based on different cohort emergence times. In the first experiment, burial at 2 cm and 5 cm decreased C. diluta emergence by 54% and 90%, respectively, compared to the emergence at 0 cm. In the second experiment, without crop-weed competition conditions, the emergence delay led to reductions in leaf number, rosette diameter, plant height and dry biomass by 63%, 50%, 59% and 93%, respectively. Seed production per plant exceeded 21 469. According to the growth model, leaf number was the most consistent morphological trait and critical for timing weed control actions, so it was used to compare SRMs and ANNs. On average, ANNs increased the precision in 5.72% (± 2.4 leaves) compared to SRMs. This slight performance of ANNs may be valuable for controlling C. diluta because control methods must be applied at the 4-leaf stage to achieve good efficacy. CONCLUSION: Seed burial at 5 cm depth is an effective method reducing C. diluta emergence. ANNs accurately predicted the leaf number employing environmental variables can help increase the efficiency of C. diluta control actions and reduce the risk of escapes. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Prevalence of Vertical Root Fractures in a University Endodontics Program versus a Private Endodontics Office.

Introduction: Vertical root fractures (VRFs) typically have a poor prognosis with an extraction or occasionally root amputation as the preferred treatment. VRFs have been considered an epidemic, motivating changes in the access openings, as well as in the preparation and disinfection protocols of endodontic treatment. Hence, we aimed to evaluate the prevalence of VRFs by tracking cases in both a University Endodontic Program (UEP) and a private endodontics practice (PP). We also evaluated changes in prevalence during COVID-19 along with the alterations in the frequency of cases diagnosed by clinical and radiographic signs which were later confirmed by direct visualization compared to those in which the suspicion was based on clinical and radiographic signs alone. Methods and Materials: This retrospective study looked at the prevalence of VRF in patient records at UEP and a PP. Data for the pre-COVID-19 and COVID-19 time periods were extracted from patient records and referral letters then compared. Data for suspected and confirmed prevalence were compared. Results: The UEP group included 21,156 patients while the PP group comprised 7,209 patients. The prevalence of VRFs in the former cohort was 1.80%, while 2.62% of the latter cohort exhibited VRFs with a combined total of 2.01%. The combined total prevalence of VRFs pre-COVID-19 was 1.72%, increasing from 2.1% to 3.82% during COVID-19 (p < 0.0001). The same applied to suspected cases for both clinical settings. The increase in confirmed cases between the two periods was statistically significant for the UEP group (p=0.0202) but it was insignificant for the PP group (p=0.0721). Conclusion: The combined prevalence for VRFs was 2.01% for all years denying the claim that VRF is a pandemic phenomenon. COVID-19 period saw almost a double increase in the prevalence of VRF compared to pre-COVID-19 era. This was consequently associated with a significant increase in the number of suspected VRF cases.

A human urothelial microtissue model reveals shared colonization and survival strategies between uropathogens and commensals.

Urinary tract infection is among the most common infections worldwide, typically studied in animals and cell lines with limited uropathogenic strains. Here, we assessed diverse bacterial species in a human urothelial microtissue model exhibiting full stratification, differentiation, innate epithelial responses, and urine tolerance. Several uropathogens invaded intracellularly, but also commensal Escherichia coli, suggesting that invasion is a shared survival strategy, not solely a virulence hallmark. The E. coli adhesin FimH was required for intracellular bacterial community formation, but not for invasion. Other shared lifestyles included filamentation (Gram-negatives), chaining (Gram-positives), and hijacking of exfoliating cells, while biofilm-like aggregates were formed mainly with Pseudomonas and Proteus. Urothelial cells expelled invasive bacteria in Rab-/LC3-decorated structures, while highly cytotoxic/invasive uropathogens, but not commensals, disrupted host barrier function and strongly induced exfoliation and cytokine production. Overall, this work highlights diverse species-/strain-specific infection strategies and corresponding host responses in a human urothelial microenvironment, providing insights at the microtissue, cell, and molecular level.

Interlaminar endoscopic uniportal approach for implantation of a paddle lead larger than 10 mm for spinal cord stimulation: illustrative case.

BACKGROUND: The authors aim to describe a new technique for implantation of a spinal cord stimulation paddle lead sized over 10 mm through an endoscopic uniportal approach. A new endoscopic cannula was developed for the passage of a paddle lead width between 10 and 13 mm. The distal portion of the cannula was designed with a larger opening, providing better visibility of the anterior portion of the adjacent structures, thus allowing a panoramic view of the electrode passage. An electrode was implanted in an 11-mm paddle. OBSERVATIONS: After searching PubMed, Cochrane, and Lilacs databases, the authors found no mention of the implantation of a paddle electrode with a width greater than 10 mm. The implantation of a paddle electrode less than 10 mm wide is possible via endoscopic access using 10-mm working channels. However, for electrodes with a width greater than 10 mm, access via endoscopy is impossible, since the working channel is only 10 mm. LESSONS: The authors concluded that it is possible to pass electrodes safely and effectively with a paddle width between 10 and 13 mm using spinal endoscopy via uniportal interlaminar access. However, it is necessary to expand studies to elucidate this technique of endoscopic implantation of electrodes for neurostimulation.

Genetic Reduction of IRF5 Expression after Disease Initiation Reduces Disease in a Mouse Lupus Model by Impacting Systemic and End-Organ Pathogenic Pathways.

Gain-of-function polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus. Global homozygous or heterozygous deficiency of IRF5 from birth confers protection in many lupus mouse models. However, less is known about the effects of IRF5 targeting after autoimmunity has already developed. This is an important point to clarify when considering IRF5 as a potential therapeutic target in lupus. In this study, we demonstrate that genetic reduction of IRF5 expression after disease initiation reduces disease severity in the FcγRIIB-/- Y-linked autoimmune accelerating mouse lupus model. Reduction of IRF5 expression resulted in a decrease in splenomegaly and lymphadenopathy and a reduction in splenic B cell activation and plasmablast numbers. Splenic T cell activation and differentiation were also impacted as demonstrated by an increase in the number of naive CD4+ and CD8+ T cells and a reduction in the number of memory/effector CD4+ and CD8+ T cells. Although serum antinuclear autoantibody levels were not altered, reduction in IRF5 expression led to decreased immune complex deposition and complement activation, diminished glomerular and interstitial disease, and a reduction in immune cell infiltrate in the kidney. Mechanistically, myeloid cells in the kidney produced less inflammatory cytokines after TLR7 and TLR9 activation. Overall, we demonstrate that genetic reduction of IRF5 expression during an active autoimmune process is sufficient to reduce disease severity. Our data support consideration of IRF5 as a therapeutic target and suggest that approaches targeting IRF5 in systemic lupus erythematosus may need to impact IRF5 activity both systemically and in target organs.

Antileishmanial effects of Crotalaria spectabilis Roth aqueous extracts on Leishmania amazonensis.

Fifteen polar extracts from leaf, seed, pod, stem, flower and root of Crotalaria spectabilis were prepared using aqueous systems, based on the principles of green chemistry, and showed different protease inhibitor (PI) activities on trypsin, papain, pepsin and the extracellular L. amazonensis serine protease (LSPIII). The most pronounced inhibitory effect on LSPIII was observed in leaf (CS-P), root, stem, flower (CS-FPVPP) and pod (CS-VA) extracts. Crotalaria extracts exhibited low cytotoxicity on macrophages; however, they decreased the viability of L. amazonensis promastigotes and amastigotes, as observed in leaf (CS-AE, CS-P, CS-T and CS-PVPP), seed (CS-ST), flower and root (CS-RA) extracts. CS-P was chosen to study PI and secondary metabolites and a 10-12 kDa protein, analyzed by mass spectrometry, was identified as a serine PI homologous with papaya latex serine PI. Glycosylated flavonoids, such as quercetins, vitexin and tricin were the major secondary metabolites of CS-P. The presence of PIs in C. spectabilis is a new finding, especially in other organs than seeds since PIs have been reported only in seed legumes. Besides, this is the first report of antileishmanial activity of C. spectabilis extracts and the identification of serine polypeptide PI and glycosylated flavonoids from leaf.

Dilution-Induced Deposition of Concentrated Binary Mixtures of Cationic Polysaccharides and Surfactants.

This work investigates the effect of dilution on the phase separation process of binary charged polysaccharide-surfactant mixtures formed by two cationic polysaccharides and up to four surfactants of different nature (anionic, zwitterionic, and neutral), as well as the potential impact of dilution-induced phase separation on the formation of conditioning deposits on charged surfaces, mimicking the negative charge and wettability of damaged hair fibers. The results obtained showed that the dilution behavior of model washing formulations (concentrated polysaccharide-surfactant mixtures) cannot be described in terms of a classical complex precipitation framework, as phase separation phenomena occur even when the aggregates are far from the equilibrium phase separation composition. Therefore, dilution-enhanced deposition cannot be predicted in terms of the worsening of colloidal stability due to the charge neutralization phenomena, as common phase separation and, hence, enhanced deposition occurs even for highly charged complexes.

Antioxidant and drought-acclimation responses in UV-B-exposed transgenic Nicotiana tabacum displaying constitutive overproduction of H2O2.

Hydrogen peroxide (H2O2) is an important molecule that regulates antioxidant responses that are crucial for plant stress resistance. Exposure to low levels of ultraviolet-B radiation (UV-B, 280-315 nm) can also activate antioxidant defenses and acclimation responses. However, how H2O2 and UV-B interact to promote stress acclimation remains poorly understood. In this work, a transgenic model of Nicotiana tabacum cv Xanthi nc, with elevated Mn-superoxide dismutase (Mn-SOD) activity, was used to study the interaction between the constitutive overproduction of H2O2 and a 14-day UV-B treatment (1.75 kJ m-2 d-1 biologically effective UV-B). Subsequently, these plants were subjected to a 7-day moderate drought treatment to evaluate the impact on drought resistance of H2O2- and UV-dependent stimulation of the plants' antioxidant system. The UV-B treatment enhanced H2O2 levels and altered the antioxidant status by increasing the epidermal flavonol index, Trolox Equivalent Antioxidant Capacity, and catalase, peroxidase and phenylalanine ammonia lyase activities in the leaves. UV-B also retarded growth and suppressed acclimation responses in highly H2O2-overproducing transgenic plants. Plants not exposed to UV-B had a higher drought resistance in the form of higher relative water content of leaves. Our data associate the interaction between Mn-SOD transgene overexpression and the UV-B treatment with a stress response. Finally, we propose a hormetic biphasic drought resistance response curve as a function of leaf H2O2 content in N. tabacum cv Xanthi.

EGF-Receptor-Dependent TLR7 Signaling in Macrophages Promotes Glomerular Injury in Crescentic Glomerulonephritis.

Glomerulonephritis (GN) is a group of inflammatory diseases and an important cause of morbidity and mortality worldwide. The initiation of the inflammatory process is quite different for each type of GN; however, each GN is characterized commonly and variably by acute inflammation with neutrophils and macrophages and crescent formation, leading to glomerular death. Toll-like receptor (TLR) 7 is a sensor for self-RNA and implicated in the pathogenesis of human and murine GN. Here, we show that TLR7 exacerbates glomerular injury in nephrotoxic serum nephritis (NTN), a murine model of severe crescentic GN. TLR7-/- mice were resistant to NTN, although TLR7-/- mice manifested comparable immune-complex deposition to wild-type mice without significant defects in humoral immunity, suggesting that endogenous TLR7 ligands accelerate glomerular injury. TLR7 was expressed exclusively in macrophages in glomeruli in GN but not in glomerular resident cells or neutrophils. Furthermore, we discovered that epidermal growth factor receptor (EGFR), a receptor-type tyrosine kinase, is essential for TLR7 signaling in macrophages. Mechanistically, EGFR physically interacted with TLR7 upon TLR7 stimulation, and EGFR inhibitor completely blocked the phosphorylation of TLR7 tyrosine residue(s). EGFR inhibitor attenuated glomerular damage in wild-type mice, and no additional glomerular protective effects by EGFR inhibitor were observed in TLR7-/- mice. Finally, mice lacking EGFR in macrophages were resistant to NTN. This study clearly demonstrated that EGFR-dependent TLR7 signaling in macrophages is essential for glomerular injury in crescentic GN.

Changes in the herbicide sensitivity and competitive ability of Abutilon theophrasti over 28 years: Implications for hormesis and weed evolution.

BACKGROUND: The potential of weed species to respond to selection forces affecting the evolution of weedy traits such as competitive ability is poorly understood. This research characterized evolutionary growth changes in a single Abutilon theophrasti Medik. population comparing multiple generations collected from 1988 to 2016. A competition study was performed to understand changes in competitive ability, and a herbicide dose-response study was carried out to assess changes in sensitivity to acetolactate synthase-inhibiting herbicides and glyphosate over time. RESULTS: When grown in monoculture, A. theophrasti biomass production per plant increased steadily across year-lines while leaf number decreased. In replacement experiments, A. theophrasti plants from newer year-lines were more competitive and produced more biomass and leaf area than the oldest year-line. No clear differences in sensitivity to imazamox were observed among year-lines. However, starting in 1995, this A. theophrasti population exhibited a progressive increase in growth in response to a sublethal dose of glyphosate (52 g a.e. ha-1 ), with the 2009 and 2016 year-lines having more than 50% higher biomass than the nontreated control. CONCLUSION: This study demonstrates that weeds can rapidly evolve increased competitive ability. Furthermore, the results indicate the possibility of changes in glyphosate hormesis over time. These results highlight the importance of the role that rapid (i.e., subdecadal) evolution of growth traits might have on the sustainability of weed management strategies. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Frontal penetrating arrow injury: A case report.

BACKGROUND: Penetrating arrow injuries of the head and neck are exceedingly rare in pediatric patients. This pathology has high morbidity and mortality because of the presence of vital organs, the airway, and large vessels. Therefore, the treatment and removal of an arrow is a challenge that requires multidisciplinary management. CASE SUMMARY: A 13-year-old boy was brought to the emergency room after an arrow injury to the frontal region. The arrowhead was lodged in the oropharynx. Imaging studies showed a lesion of the paranasal sinuses without compromising vital structures. The arrow was successfully removed by retrograde nasoendoscopy without complications, and the patient was discharged. CONCLUSION: Although rare, maxillofacial arrow injuries have high morbidity and mortality and require multidisciplinary management to preserve function and aesthetics.

Plant hormesis: Revising of the concepts of biostimulation, elicitation and their application in a sustainable agricultural production.

Current research in basic and applied knowledge of plant science has aimed to unravel the role of the interaction between environmental factors and the genome in the physiology of plants to confer the ability to overcome challenges in a climate change scenario. Evidence shows that factors causing environmental stress (stressors), whether of biological, chemical, or physical origin, induce eustressing or distressing effects in plants depending on the dose. The latter suggests the induction of the "hormesis" phenomenon. Sustainable crop production requires a better understanding of hormesis, its basic concepts, and the input variables to make its management feasible. This implies that acknowledging hormesis in plant research could allow specifying beneficial effects to effectively manage environmental stressors according to cultivation goals. Several factors have been useful in this regard, which at low doses show beneficial eustressing effects (biostimulant/elicitor), while at higher doses, they show distressing toxic effects. These insights highlight biostimulants/elicitors as tools to be included in integrated crop management strategies for reaching sustainability in plant science and agricultural studies. In addition, compelling evidence on the inheritance of elicited traits in plants unfolds the possibility of implementing stressors as a tool in plant breeding.

Characterization of the Key Compounds of Bell Pepper by Spectrophotometry and Gas Chromatography on the Effects of Induced Stress on the Concentration of Secondary Metabolite.

Sweet peppers are consumed worldwide, and traditional uses have sparked interest in their applications as dietary antioxidants, which can be enhanced in plants using elicitors. These are endowed with phytochemicals with potential health benefits such as antioxidants, bioavailability, and bioaccessibility. The trend in metabolomics shows us chemical fingerprints linking metabolomics, innovative analytical form, and bioinformatics tools. The objective was to evaluate the impact of multiple stress interactions, elicitor concentrations, and electrical conductivity on the concentration of secondary metabolites to relate their response to metabolic pathways through the foliar application of a cocktail of said elicitors in pepper crops under greenhouse conditions. The extracts were analyzed by spectrophotometry and gas chromatography, and it was shown that the PCA analysis identified phenolic compounds and low molecular weight metabolites, confirming this as a metabolomic fingerprint in the hierarchical analysis. These compounds were also integrated by simultaneous gene and metabolite simulants to obtain effect information on different metabolic pathways. Showing changes in metabolite levels at T6 (36 mM H2O2 and 3.6 dS/m) and T7 (0.1 mM SA and 3.6 dS/m) but showing statistically significant changes at T5 (3.6 dS/m) and T8 (0.1 mM SA, 36 mM H2O2, and 3.6 dS/m) compared to T1 (32 dS/m) or control. Six pathways changed significantly (p < 0.05) in stress-induced treatments: aminoacyl t-RNA and valine-leucine-isoleucine biosynthesis, and alanine-aspartate-glutamate metabolism, glycoxylate-dicarboxylate cycle, arginine-proline, and citrate. This research provided a complete profile for the characterization of metabolomic fingerprint of bell pepper under multiple stress conditions.

Pelvic lymph node dissection for cervical or bladder cancer: embedding residual fat tissue offers no added value.

Diagnosis of lymph node metastases in pelvic lymph node dissection (PLND) is important for staging and treatment. Standard practice is to submit visible or palpable lymph nodes for histology. We assessed the added value of embedding all residual fatty tissue.Patients (n = 85) who underwent PLND for cervical (n = 50) or bladder cancer (n = 35) between 2017 and 2019 were included. Study approval was obtained (MEC-2022-0156, 18.03.2022, retrospectively registered).The median lymph node yield with conventional pathological dissection was 21 nodes (Interquartile range (IQR) 18-28). This led to discovery of positive lymph nodes in 17 (20%) patients. Extended pathological assessment found 7 (IQR 3-12) additional nodes, but did not result in identification of more node metastases.Histopathological analysis of residual fatty tissue harvested at PLND resulted in an increased lymph node yield, but not in the detection of additional lymph node metastases.

Understanding Progestins: From Basics to Clinical Applicability.

Progestin is a term used to describe a synthetic progestogen. The activity and potency of synthetic progestins are mostly evaluated via parameters associated with their endometrial effects, which are related to their interactions with progesterone, estrogen, androgen, glucocorticoid, and mineralocorticoid receptors. The chemical structure of progestins is the key to understanding their interactions with these receptors and predicting the other effects associated with these drugs. Due to their endometrial effect, progestins are used for different gynecological conditions, such as endometriosis, contraception, hormonal replacement therapy, and artificial reproduction techniques. This review is focused on improving our knowledge of progestins (from their history and biochemical effects related to their chemical structures to clinical applications in gynecological conditions) in order to improve clinical practice.

Layer-by-Layer Nanoassemblies for Vaccination Purposes.

In recent years, the availability of effective vaccines has become a public health challenge due to the proliferation of different pandemic outbreaks which are a risk for the world population health. Therefore, the manufacturing of new formulations providing a robust immune response against specific diseases is of paramount importance. This can be partially faced by introducing vaccination systems based on nanostructured materials, and in particular, nanoassemblies obtained by the Layer-by-Layer (LbL) method. This has emerged, in recent years, as a very promising alternative for the design and optimization of effective vaccination platforms. In particular, the versatility and modularity of the LbL method provide very powerful tools for fabricating functional materials, opening new avenues on the design of different biomedical tools, including very specific vaccination platforms. Moreover, the possibility to control the shape, size, and chemical composition of the supramolecular nanoassemblies obtained by the LbL method offers new opportunities for manufacturing materials which can be administered following specific routes and present very specific targeting. Thus, it will be possible to increase the patient convenience and the efficacy of the vaccination programs. This review presents a general overview on the state of the art of the fabrication of vaccination platforms based on LbL materials, trying to highlight some important advantages offered by these systems.