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Constantine E Kosmas,1 Delia Silverio,2 Julio Ovalle,2 Peter D Montan,2 Eliscer Guzman3 1Division of Cardiology, Department of Medicine, Mount Sinai Hospital, New York, NY, USA; 2Cardiology Clinic, Cardiology Unlimited, PC, New York, NY, USA; 3Division of Cardiology, Department of Medicine, Montefiore Medical Center, Bronx, NY, USA Abstract: Evolocumab is a PCSK9 inhibitor which is administered subcutaneously, and when added to statin therapy it has been shown to cause a significant incremental LDL-C reduction, leading to a reduction of cardiovascular risk. Evolocumab has a favorable side effect profile, and its self-administration at home appears to be safe and effective with the appropriate training and instructions from a health care provider. Current studies are showing encouraging results regarding adherence to evolocumab in real-life settings, and adherence rates to evolocumab appear to be better than those to statins. However, further larger studies are needed for a more definitive assessment of the short- and long-term patient adherence rates to evolocumab. In addition, reductions in the price of evolocumab may also be necessary to improve cost-effectiveness of the drug. Keywords: evolocumab, adherence, hypercholesterolemia, cardiovascular risk

Abstract Background Given the increasing frequency of disasters globally, it is critical that healthcare systems are prepared for these mass casualty events. The Saudi health system’s preparedness for mass casualty incidents needs to be more robust, potentially due to limited disaster drills and inadequate standardized patient (SP) simulation training. This study aims to (i) assess the performance of front-line hospital staff in Saudi Arabia through a functional drill and (ii) evaluate the drill’s effectiveness using SP and MAC-SIM cards, providing detailed insights into its design and execution. Methods A functional drill was conducted at a government hospital in Riyadh, Saudi Arabia, on December 19, 2022, using a cross-sectional approach with two phases. 141 healthcare receivers served as subjects, while 23 volunteers acted as SPs. The scenario simulated a building collapse to assess the emergency department (ED) response, interdepartmental communication, and surge capacity. Data were collected through direct observation of healthcare practitioners’ interactions with the SPs, analysis of SP data, and participant feedback. Quantitative data were analyzed descriptively, while qualitative data were examined for patterns and themes related to simulation performance and effectiveness. Results The hospital receivers’ performances demonstrated accurate triage categories. The ED team assessed most patients (67%) in less than 5 min. For patients requiring definitive care, such as intensive care unit, 95% spent less than 2.5 h in the ED. Most patients (65%) required ‘other treatments’. Communication was efficient in the triage zone and the yellow treatment area. Participants’ feedback on using MAC-SIM cards during the simulation was overwhelmingly positive with 82.61% reporting that MAC-SIM use helped them respond better. Experienced SPs (paramedics) with prior disaster knowledge and experience outperformed inexperienced SPs (nurses) in the functional exercise. Conclusion This groundbreaking study is the first in the Arabic Gulf region to use SPs with MAC-SIM cards in functional drills. The findings highlight the potential of simulation exercises to improve hospital team knowledge and performance when responding to disasters. Multiple evaluation techniques can effectively identify participant strengths and weaknesses, informing future disaster improvement plans. This information is a valuable resource for Arabic and middle-income countries where disaster medicine is still developing.

ABSTRACT Searching for novel sources of resistance to head blast is essential to strengthen wheat production in the Cerrado´s biome. The objective of this work was to evaluate disease intensity measures and yield for 2NS and non-2NS carriers wheat genotypes with varying heading times in Minas Gerais, Brazil. A total of fourteen wheat genotypes, two susceptible and twelve resistant to head blast, were sown in 2014, 2015, and 2017 at the Sertãozinho Experimental Station of Empresa de Pesquisa Agropecuária de Minas Gerais (Epamig) during three sowing dates without fungicide applications. The experimental design was a randomized complete block with three replicates. Blast incidence, severity, disease index and grain yield were influenced by the cycle of wheat genotypes and the sowing date, with the highest disease intensities and the lowest yields in the earliest sowing date. Blast incidence and disease index correlated negatively with grain yield and positively with percent yield losses. The group of wheat genotypes with higher grain yield (between 2,104.7 and 2,917.8 kg ha-1) and lower yield losses (between 44.3 and 54.8%) includes BR 18 as well as other five that do not carry the 2NS/2AS translocation: BRS Angico, PF 909, BRS 229, Embrapa 27, and CPAC 07340.

Lidocaine is the most commonly used local anesthetic worldwide, known for its rapid onset and moderate duration of anesthesia. However, it is short-lived and does not effectively promote effective topical anesthesia in the oral cavity when used alone. Our aim was to investigate whether an approximate 50% encapsulation of lidocaine in poly(ε-caprolactone) nanocapsules (LDC-Nano) would be able to increase its permeation and analgesic efficacy and reduce cytotoxicity. In this study, we characterized LDC-Nano and conducted MTT tests with HaCaT cells to assess their in vitro cytotoxicity. Additionally, in vitro permeation assays across the pig esophageal epithelium and the anesthetic efficacy of the hind paw incision model in rats were performed. Plain lidocaine (LDC) was compared with LDC-Nano and lidocaine hydrochloride plus epinephrine (LDC-Epi). The physicochemical characteristics of LDC-Nano were satisfactory (pH: 8.1 ± 0.21; polydispersity index: 0.08 ± 0.01; mean diameter (nm): 557.8 ± 22.7; and encapsulation efficiency (%): 51.8 ± 1.87) and remained stable for up to 4 months. LDC-Nano presented similar in vitro cytotoxicity to LDC but was higher than LDC-Epi (LD50: LDC = 0.48%; LDC-Nano = 0.47%; and LDC-Epi = 0.58%; p < 0.0001). Encapsulation increased the permeability coefficient about 6.6 times and about 7.5 the steady-state flux of lidocaine across the mucosal epithelium. Both encapsulation and epinephrine improved anesthesia duration, with epinephrine demonstrating superior efficacy (100% of animals were anesthetized up to 100, 30, and 20 min when LDC-Epi, LDC-nano, and LDC were used, respectively). Although LDC-Epi demonstrated superior in vivo anesthetic efficacy, the in vitro permeation and cytotoxicity of LDC-Nano indicate promising avenues for future research, particularly in exploring its potential application as a topical anesthetic in the oral cavity.

Abstract The objective of this work was to evaluate the effect of the presence of 2NVS translocation on the inheritance of wheat resistance to head blast, in F2 segregating lines from two biparental crosses. The IPF 86766 and 'Santa Fe' genotypes were used as female parents (both 2NVS carriers), and 'BRS 404', as the common male parent (non 2NVS carrier). Using a mixture of three isolates of Pyricularia oryzae Triticum, wheat spikes and rachises were evaluated for bleaching severity at five (%BS_5dpi) and seven days post-inoculation (%BS_7dpi), as well as for the number of infection points (IPR) and pathogen sporulation (SPO). Chi-square analyses showed that segregation follows a 3:1 Mendelian hypothesis, with a major locus with a dominant allele: %BS_7dpi for IPF 86766 × 'BRS 404' and IPR for 'Santa Fe' x 'BRS 404'. Therefore, this is the first known study to show that the 2NVS translocation responsible for resistance to head blast is a major locus with a dominant allele. In a controlled environment, 'BRS 404' shows bleaching severity and SPO similar with those occurring on IPF 86766 and 'Santa Fe'.

Locke argued that persons born blind do not possess true knowledge about color. While prior studies find some knowledgeof color among blind individuals, questions remain about the depth of this knowledge. Do blind individuals merely learninferentially shallow verbal associations (e.g., bananayellow)? We hypothesized instead that blind individuals are morelikely to acquire causally-relevant color information. Blind (n=20) and sighted adults (n=20) reported colors of naturalkinds (e.g. banana) and artifacts (e.g. car) and judged the likelihood that two instances of a type have the same color.Relative to the sighted, blind participants were less likely to know specific object colors (e.g. banana-yellow), but madeidentical inferences about color consistency (more consistent colors for natural kinds). Inferences were similar acrossgroups even for novel objects. Further, blind individuals gave detailed and coherent causal explanations of color origins.Inferentially rich knowledge of sensory categories can develop without first-person experience.

This randomized placebo-controlled crossover trial evaluated if nanostructured lipid nanocarriers (NLC) could improve the topical anaesthetic efficacy of lidocaine and prilocaine (L+P) incorporated in a xanthan-hydrogel applied in the oral cavity. There were no differences among topical formulations regarding the primary endpoints of pain intensity during needle insertion or local anaesthetic injection. Nonetheless, exploratory analyses indicate that individuals with low mechanical pain sensitivity were more susceptible to placebo effects which could also interfere with the anaesthetic effects of the topical formulations. Thus, mechanical pain sensitivity can be an interesting approach to increase assay sensitivity in clinical trials of topical anaesthesia.

Objective: The scientific community has recently directed its attention towards investigating the role of androgens in female sexuality. This narrative review aims to elucidate the central and peripheral androgen-mediated mechanisms involved in female sexual health and function. Additionally, the current state of androgen therapeutic options is discussed. Mechanism: We searched several scientific literature databases, including EMBASE, MEDLINE, PubMed Central, and Scopus, utilizing keywords, index terms, and MeSH terms, such as “androgen*”, “female sexuality”, “female sexual function”, “women’s sexual dysfunctions”, “androgen therapy in women”, and various combinations thereof. Findings in Brief: Progesterone or estrogens are commonly prescribed as first-line treatments for female sexual dysfunctions. However, these medications may frequently lead to therapeutic failure and cause harm by increasing sex-hormone-binding-globulin plasma levels and decreasing testosterone plasma concentrations. Currently, there are limited androgen therapies available for women, and the evidence for their effectiveness and safety is still limited. Conclusions: The knowledge of neuroendocrine interactions that underlie sexual arousal and pleasure is rapidly expanding, and ongoing research is striving to develop more appropriate clinical practices for managing sexual dysfunctions in women.

Abstract Background The Swedish National Cataract Register (NCR) collects data on cataract surgery outcomes during March, including patient-reported outcomes using the Catquest-9SF questionnaire for over 11 years. Previous studies from NCR have shown that the preoperative visual acuity has improved over time. The main purpose of this study was to evaluate the Catquest-9SF Rasch scoring performance in this changing environment. A second purpose was to describe clinical data over the same period for those who completed the questionnaire. Methods The performance of the Catquest-9SF was analysed by a separate Rasch analysis for each year, resulting in a preoperative and postoperative score for each participating patient in the annual cohorts. The clinical data and questionnaire scoring were analysed for each year in the period 2008–2018 inclusive. Results Data were available for 42,023 eyes for 11 annual cohorts (2008–2018). The psychometric properties of the questionnaire were stable during the study period. Person separation (precision) for the whole period was 2.58 and varied between 2.45 and 2.72. The person reliability was 0.87 and varied between 0.86 and 0.88. The targeting of question difficulty to person ability became less accurate over time meaning that the item activities became easier to carry out without difficulty. The average targeting for the whole period was −2.06 and changed from −1.92 in 2008 to −2.31 in 2018. The person score improved both before surgery and after surgery, indicating that patients are undergoing surgery at a more able level and getting better outcomes. The average improvement by surgery decreased from 3.41 logits in 2008 to 3.21 logits in 2018 (p = 0.003). Over time, patient age decreased from 75 to 74 years (p

Abstract This review paper presents the current context of wheat production in Brazil, the management strategies to reduce yield losses due to blast, and the biotechnological approaches to improve wheat resistance. Wheat blast or brusone is caused by the Magnaporthe oryzae Triticum (MoT) pathotype fungus that can infect all the aboveground parts of the plant. The main symptom of the blast disease is spike bleaching that impairs grain production, causing yield losses up to 100% in susceptible wheat cultivars. The first world report of blast in wheat spikes was in Brazil, in 1985, and, currently, the disease is the main constraint to wheat cultivation in tropical and subtropical areas of the Cerrado and Mata Atlântica biomes. For a long time, the use of fungicides has been found to be ineffective under high-pressure disease conditions. However, recent works have pointed out that fungicide efficiency depends on the integration of other control measures, particularly the choice of cultivars with moderate resistance. In this review paper, the high variability of wheat reaction to MoT is presented, as well as a panel of resistant or moderately resistant cultivars (including non-2NS carriers), promptly available for cultivation in regions where blast is endemic.

Abstract Background Wheat blast, caused by Magnaporthe oryzae Triticum (MoT) pathotype, is a global threat to wheat (Triticum aestivum L.) production. Few blast resistance (R) genes have been identified to date, therefore assessing potential sources of resistance in wheat is important. The Brazilian wheat cultivar BR 18-Terena is considered one of the best sources of resistance to blast and has been widely used in Brazilian breeding programmes, however the underlying genetics of this resistance are unknown. Results BR 18-Terena was used as the common parent in the development of two recombinant inbred line (RIL) F6 populations with the Brazilian cultivars Anahuac 75 and BRS 179. Populations were phenotyped for resistance at the seedling and heading stage using the sequenced MoT isolate BR32, with transgressive segregation being observed. Genetic maps containing 1779 and 1318 markers, were produced for the Anahuac 75 × BR 18-Terena and BR 18-Terena × BRS 179 populations, respectively. Five quantitative trait loci (QTL) associated with seedling resistance, on chromosomes 2B, 4B (2 QTL), 5A and 6A, were identified, as were four QTL associated with heading stage resistance (1A, 2B, 4A and 5A). Seedling and heading stage QTL did not co-locate, despite a significant positive correlation between these traits, indicating that resistance at these developmental stages is likely to be controlled by different genes. BR 18-Terena provided the resistant allele for six QTL, at both developmental stages, with the largest phenotypic effect conferred by a QTL being 24.8% suggesting that BR 18-Terena possesses quantitative resistance. Haplotype analysis of 100 Brazilian wheat cultivars indicates that 11.0% of cultivars already possess a BR 18-Terena-like haplotype for more than one of the identified heading stage QTL. Conclusions This study suggests that BR 18-Terena possesses quantitative resistance to wheat blast, with nine QTL associated with resistance at either the seedling or heading stage being detected. Wheat blast resistance is also largely tissue-specific. Identification of durable quantitative resistances which can be combined with race-specific R gene-mediated resistance is critical to effectively control wheat blast. Collectively, this work facilitates marker-assisted selection to develop new varieties for cultivation in regions at risk from this emerging disease.

Bread wheat (Triticum aestivum L.) is one of the world’s most important crops. Maintaining wheat yield gains across all of its major production areas is a key target toward underpinning global food security. Brazil is a major wheat producer in South America, generating grain yields of around 6.8 million tons per year. Here, we establish and genotype a wheat association mapping resource relevant to contemporary Brazilian wheat breeding programs. The panel of 558 wheat accessions was genotyped using an Illumina iSelect 90,000 single nucleotide polymorphism array. Following quality control, the final data matrix consisted of 470 accessions and 22,475 polymorphic genetic markers (minor allele frequency ≥5%, missing data

There are several routes of drug administration, and each one has advantages and limitations. In the case of the topical application in the oral cavity, comprising the buccal, sublingual, palatal, and gingival regions, the advantage is that it is painless, non-invasive, allows easy application of the formulation, and it is capable of avoiding the need of drug swallowing by the patient, a matter of relevance for children and the elderly. Another advantage is the high permeability of the oral mucosa, which may deliver very high amounts of medication rapidly to the bloodstream without significant damage to the stomach. This route also allows the local treatment of lesions that affect the oral cavity, as an alternative to systemic approaches involving injection-based methods and oral medications that require drug swallowing. Thus, this drug delivery route has been arousing great interest in the pharmaceutical industry. This review aims to condense information on the types of biomaterials and polymers used for this functionality, as well as on production methods and market perspectives of this topical drug delivery route.

Smoke taint has become a prominent issue for the global wine industry as climate change continues to impact the length and extremity of fire seasons around the world. When grapevines are exposed to smoke, their leaves and fruit can adsorb volatile smoke compounds (for example, volatile phenols such as guaiacol, 4-methylguaiacol, o-, m- and p-cresol, and syringol), which can initially be detected in free (aglycone) forms but are rapidly converted to glycoconjugate forms due to glycosylation. During the fermentation process, these glycoconjugates can be broken down, releasing volatile phenols that contribute undesirable sensory characteristics to the resultant wine (i.e. smokey and ashy attributes). Several methods have been evaluated, both viticultural measures and winemaking techniques, for mitigating and/or remediating the negative effects of grapevine smoke exposure. While there is currently no single method that universally solves the problem of smoke taint, this paper outlines the tools available that can help to minimize the negative impacts of smoke taint (Figure 1).

Large datasets are highly valuable resources to investigate multi-scale patterns of organisms, and lay foundations for citizen science-based conservation strategies. Here, we used 1,043,262 records from 1708 to 2021 to explore the geography, taxonomy, ecology and distribution patterns of 11,556 fungal taxa in metropolitan France. Our analysis reveals a four-phase pattern of temporal recording, with a main contribution of post-1977 observations in relation with the structuration of associative mycology. The dataset shows an uneven geography of fungal recording. Four clusters of high-intensity sampling scattered across France contrast with poorly documented areas, including the Mediterranean. Basidiomycota and Agaricales highly dominate the dataset, accounting for 88.8 and 50.4% of records, respectively. The dataset is composed of many rare taxa, with 61.2% of them showing fewer than 100 records, and 20.5% recorded only once. The analysis of metadata brings to light a preponderance of the mycorrhizal guild (44.6%), followed by litter saprotrophs (31.6%) and wood saprotrophs (18.1%). Highly documented forests (76.3% of records) contrast with poorly investigated artificial (6.43%) and open habitats (10.1%). This work provides the first comprehensive overview of fungal diversity in France and identifies the Mediterranean area and open habitats as priorities to integrate into a global strategy for fungal conservation in France.

Calcific aortic valve stenosis is the most common valve disease in the elderly population and is associated with significant morbidity and mortality. This condition is characterised by gradual fibrosis, thickening, and calcification of the affected leaflets, leading to decreased leaflet mobility and increased obstruction of the blood flow from the left ventricle. Lipoprotein(a) [Lp(a)] is a complex polymorphic lipoprotein with proatherogenic, proinflammatory, and prothrombotic properties. Several epidemiologic and clinical studies have described elevated Lp(a) levels as an independent causative risk factor for cardiovascular disease, including coronary artery disease, stroke, peripheral artery disease, heart failure, and venous thromboembolism. On the other hand, several studies have also described Lp(a) as a strong genetic causative risk factor for aortic valve calcification and aortic valve stenosis. In this review, the authors present and discuss the scientific and clinical evidence pertaining to the role of Lp(a) in calcific aortic valve stenosis.

Aims To investigate changes in the prescribing patterns of postoperative eye drops following cataract surgery in Sweden from 2010 to 2017.Methods Data from cataract procedures registered in the National Cataract Register during the month of March from 2010 to 2017 were record linked and sent to the Swedish Prescribed Drug Register, which allowed us to determine which eye drops the patients had obtained from 3 months presurgery to 2 weeks post surgery.Results During the 8-year study period, 54 889 surgeries were registered. Combination treatment with steroid and non-steroidal anti-inflammatory drug (NSAID) eye drops increased from 12% in 2010 to 60% in 2017 (p

To determine whether the permeation capacity and analgesic efficacy of articaine (ATC) could be increased and cytotoxicity decreased by encapsulation in poly(ɛ-caprolactone) nanocapsules (ATCnano), aiming at local or topical anesthesia in dentistry. Cellular viability was evaluated (using the MTT test and fluorescence microscopy) after 1 h and 24 h exposure of HaCaT cells to ATC, ATCnano, ATC with epinephrine (ATCepi), and ATC in nanocapsules with epinephrine (ATCnanoepi). The profiles of permeation of 2% ATC and 2% ATCnano across swine esophageal epithelium were determined using Franz-type vertical diffusion cells. Analgesic efficacy was evaluated with a von Frey anesthesiometer in a postoperative pain model in rats, comparing the 2% ATC, 2% ATCnano, 2% ATCepi, and 2% ATCnanoepi formulations to 4% ATCepi (a commercially available formulation). We show that use of the nanocapsules decreased the toxicity of articaine (P

Fusarium head blight (FHB) is a disease of wheat (Triticum aestivum L.) that causes major yield losses in South America, as well as many other wheat growing regions around the world. FHB results in low quality, contaminated grain due to the production of mycotoxins such as deoxynivalenol (DON). In Brazil, FHB outbreaks are increasing in frequency and are currently controlled by fungicides which are costly and potentially harmful to the wider environment. To identify the genetic basis of resistance to FHB in Brazilian wheat, two mapping populations (Anahuac 75 × BR 18-Terena and BR 18-Terena × BRS 179) segregating for FHB resistance were phenotyped and quantitative trait loci (QTL) analysis was undertaken to identify genomic regions associated with FHB-related traits. A total of 14 QTL associated with FHB visual symptoms were identified, each of which explained 3.7-17.3% of the phenotypic variance. Two of these QTL were stable across environments. This suggests FHB resistance in Anahuac 75, BR 18-Terena and BRS 179 is controlled by multiple genetic loci that confer relatively minor differences in resistance. A major, novel QTL associated with DON accumulation was also identified on chromosome 4B (17.8% of the phenotypic variance), as well as a major QTL associated with thousand-grain weight on chromosome 6B (16.8% phenotypic variance). These QTL could be useful breeding targets, when pyramided with major sources of resistance such as Fhb1, to improve grain quality and reduce the reliance on fungicides in Brazil and other countries affected by FHB.

There is extensive evidence demonstrating that there is a clear inverse correlation between plasma high density lipoprotein cholesterol (HDL-C) concentration and cardiovascular disease (CVD). On the other hand, there is also extensive evidence that HDL functionality plays a very important role in atheroprotection. Thus, genetic disorders altering certain enzymes, lipid transfer proteins, or specific receptors crucial for the metabolism and adequate function of HDL, may positively or negatively affect the HDL-C levels and/or HDL functionality and subsequently either provide protection or predispose to atherosclerotic disease. This review aims to describe certain genetic disorders associated with either low or high plasma HDL-C and discuss their clinical features, associated risk for cardiovascular events, and treatment options.

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Recent advances have been reported for needle-free local anesthesia in maxillary teeth by administering a nasal spray of tetracaine (TTC) and oxymetazoline, without causing pain, fear, and stress. This work aimed to assess whether a TTC-loaded hybrid system could reduce cytotoxicity, promote sustained permeation, and increase the anesthetic efficacy of TTC for safe, effective, painless, and prolonged analgesia of the maxillary teeth in dental procedures. The hybrid system based on TTC (4%) encapsulated in nanostructured lipid carriers (NLC) and incorporated into a thermoreversible hydrogel of poloxamer 407 (TTCNLC-HG4%) displayed desirable rheological, mechanical, and mucoadhesive properties for topical application in the nasal cavity. Compared to control formulations, the use of TTCNLC-HG4% slowed in vitro permeation of the anesthetic across the nasal mucosa, maintained cytotoxicity against neuroblastoma cells, and provided a three-fold increase in analgesia duration, as observed using the tail-flick test in mice. The results obtained here open up perspectives for future clinical evaluation of the thermoreversible hybrid hydrogel, which contains TTC-loaded NLC, with the aim of creating an effective, topical, intranasal, needle-free anesthesia for use in dentistry.

BackgroundYoung people living with juvenile idiopathic arthritis (JIA) face a number of communication barriers for achieving optimal health as they transition from pediatric care into adult care. Despite growing interest in mobile or wireless technologies to support health (mHealth), it is uncertain how these engagement tools might support young people, their families, and care teams to optimize preference-based treatment strategies. ObjectiveThis study aims to examine how an mHealth patient support system (mPSS) might foster partnership between young people living with JIA, their families, and care teams. MethodsSemistructured interviews with young people (5-15 years old), their families, and JIA care teams were conducted using researcher-developed interviews guides. Transcribed data were qualitatively analyzed using conventional content analysis. ResultsWe conducted semistructured interviews with 15 young people, their parents, and 4 care team members. Content analysis revealed the potential of an mPSS to support productive dialogue between families and care teams. We identified four main themes: (1) young people with JIA face communication challenges, (2) normalizing illness through shared experience may improve adherence, (3) partnership opens windows into illness experiences, and (4) readiness to engage appears critical for clinic implementation. ConclusionsA human-centered mPSS design that offers JIA patients the ability to track personally relevant illness concerns and needs can enhance communication, generate consensus-based treatment decisions, and improve efficiency and personalization of care. Technology that supports continuous learning and promotes better understanding of disease management may reduce practice burden while increasing patient engagement and autonomy in fostering lasting treatment decisions and ultimately supporting personalized care and improving outcomes.

Permeation assays are important for the development of topical formulations applied on buccal mucosa. Swine buccal and esophageal epithelia are usually used as barriers for these assays, while frozen epithelia have been used to optimize the experimental setup. However, there is no consensus on these methods. In transdermal studies, barrier integrity has been evaluated by measuring electrical resistance (ER) across the skin, which has been demonstrated to be a simple, fast, safe, and cost-effective method. Therefore, the aims here were to investigate whether ER might also be an effective method to evaluate buccal and esophageal epithelium mucosa integrity for in vitro permeation studies, and to establish a cut-off ER value for each epithelium mucosa model. We further investigated whether buccal epithelium could be substituted by esophageal epithelium in transbuccal permeation studies, and whether their permeability and integrity were affected by freezing at −20 °C for 3 weeks. Fresh and frozen swine buccal and esophageal epithelia were mounted in Franz diffusion cells and were then submitted to ER measurement. Permeation assays were performed using lidocaine hydrochloride as a hydrophilic drug model. ER was shown to be a reliable method for evaluating esophageal and buccal epithelia. The esophageal epithelium presented higher permeability compared to the buccal epithelium. For both epithelia, freezing and storage led to decreased electrical resistivity and increased permeability. We conclude that ER may be safely used to confirm tissue integrity when it is equal to or above 3 kΩ for fresh esophageal mucosa, but not for buccal epithelium mucosa. However, the use of esophageal epithelium in in vitro transmucosal studies could overestimate the absorption of hydrophilic drugs. In addition, fresh samples are recommended for these experiments, especially when hydrophilic drugs are involved.

Smoke taint has become a prominent issue for the global wine industry as climate change continues to impact the length and extremity of fire seasons around the world. Although the issue has prompted a surge in research on the subject in recent years, no singular solution has yet been identified that is capable of maintaining the quality of wine made from smoke-affected grapes. In this review, we summarize the main research on smoke taint, the key discoveries, as well as the prevailing uncertainties. We also examine methods for mitigating smoke taint in the vineyard, in the winery, and post production. We assess the effectiveness of remediation methods (proposed and actual) based on available research. Our findings are in agreement with previous studies, suggesting that the most viable remedies for smoke taint are still the commercially available activated carbon fining and reverse osmosis treatments, but that the quality of the final treated wines is fundamentally dependent on the initial severity of the taint. In this review, suggestions for future studies are introduced for improving our understanding of methods that have thus far only been preliminarily investigated. We select regions that have already been subjected to severe wildfires, and therefore subjected to smoke taint (particularly Australia and California) as a case study to inform other wine-producing countries that will likely be impacted in the future and suggest specific data collection and policy implementation actions that should be taken, even in countries that have not yet been impacted by smoke taint. Ultimately, we streamline the available information on the topic of smoke taint, apply it to a global perspective that considers the various stakeholders involved, and provide a launching point for further research on the topic.

Ropivacaine is a local anesthetic with similar potency but lower systemic toxicity than bupivacaine, the most commonly used spinal anesthetic. The present study concerns the development of a combined drug delivery system for ropivacaine, comprised of two types of liposomes: donor multivesicular vesicles containing 250 mM (NH4)2SO4 plus the anesthetic, and acceptor large unilamellar vesicles with internal pH of 5.5. Both kinds of liposomes were composed of hydrogenated soy-phosphatidylcholine:cholesterol (2:1 mol%) and were prepared at pH 7.4. Dynamic light scattering, transmission electron microscopy and electron paramagnetic resonance techniques were used to characterize the average particle size, polydispersity, zeta potential, morphology and fluidity of the liposomes. In vitro dialysis experiments showed that the combined liposomal system provided significantly longer (72 h) release of ropivacaine, compared to conventional liposomes (~45 h), or plain ropivacaine (~4 h) (p

The use of biomaterials composed of organic pristine components has been successfully described in several purposes, such as tissue engineering and drug delivery. Drug delivery systems (DDS) have shown several advantages over traditional drug therapy, such as greater therapeutic efficacy, prolonged delivery profile, and reduced drug toxicity, as evidenced by in vitro and in vivo studies as well as clinical trials. Despite that, there is no perfect delivery carrier, and issues such as undesirable viscosity and physicochemical stability or inability to efficiently encapsulate hydrophilic/hydrophobic molecules still persist, limiting DDS applications. To overcome that, biohybrid systems, originating from the synergistic assembly of polymers and other organic materials such as proteins and lipids, have recently been described, yielding molecularly planned biohybrid systems that are able to optimize structures to easily interact with the targets. This work revised the biohybrid DDS clarifying their advantages, limitations, and future perspectives in an attempt to contribute to further research of innovative and safe biohybrid polymer-based system as biomaterials for the sustained release of active molecules.

PURPOSE:To develop an anesthetic mucoadhesive film containing Acmella oleracea (jambu) extract for topical use on oral mucosa. METHODS:Ethanolic extracts from aerial parts of jambu were prepared by maceration. Pigment removal was obtained by adsorption with activated carbon. Three mucoadhesive films were developed using a film casting method: 10 or 20% of crude jambu extract (10% JB and 20% JB), and 10% of crude jambu extract treated with activated carbon (10% JBC). The mucoadhesive films were characterized regarding their uniformity, thickness, pH, and spilanthol content, and their stability was evaluated during 120 days. Gas chromatography was used to quantify the amount of spilanthol. In vitro tests determined the permeation of spilanthol across pig esophageal epithelium mucosa in Franz diffusion cells. Topical anesthetic efficacy was assessed in vivo using a tail flick test in mice. RESULTS:The three mucoadhesive films showed physical stability and visual appearances suitable for use on oral mucosa. The permeation study revealed that the spilanthol from 10% JBC presented higher flux and permeability coefficient values, compared to 10% or 20% JB (p < 0.001). Moreover, 10% JBC showed better topical anesthetic efficacy than the other films (p < 0.01). CONCLUSION:Mucoadhesive film containing crude extract of jambu treated with activated carbon is a potential alternative for oral, topical use, encouraging future clinical studies.