Room temperature two terminal tunnel magnetoresistance in a lateral graphene transistor.

We investigate the behavior of both pure spin and spin-polarized currents measured with four-probe non-local and two probe local configurations up to room temperature and under an external gate voltage in a lateral graphene transistor, produced using a standard large-scale microfabrication process. The high spin diffusion length of pristine graphene in the channel, measured both directly and by the Hanle effect, and the tuning of the relationship between the electrode resistance areas present in the device architecture allowed us to observe local tunnel magnetoresistance at room temperature, a new finding for this type of device. The results also indicate that while pure spin currents are less sensitive to temperature variations, spin-polarized current switching by an external voltage is more efficient, due to a combination of the Rashba effect and a change in carrier mobility by a Fermi level shift.

Effect of albumin, urea, lysozyme and mucin on the triboactivity of Ti6Al4V/zirconia pair used in dental implants.

The titanium implant/zirconia abutment interface can suffer failure upon mechanical and biological issues, ultimately leading to the loss of the artificial tooth. The study of the effect of the organic compounds present in saliva on the tribological behavior of these systems is of utmost importance to understand the failure mechanisms and better mimic the in vivo conditions. The aim of the present work is to evaluate the effect of the addition of albumin, urea, lysozyme and mucin to artificial saliva, on the triboactivity of Ti6Al4V/zirconia pair commonly used in dental implants and then, compare the results with those obtained with human saliva. The solutions' viscosity was measured and the adsorption of the different biomolecules to both Ti6Al4V and zirconia was accessed. Tribological tests were performed using Ti6Al4V balls sliding on zirconia plates inside of a corrosion cell. Friction and wear coefficients were determined, and the open circuit potential (OCP) was monitored during the tests. Also, the wear mechanisms were identified. The presence of mucin in the artificial lubricant led to the lowest wear coefficients. The main wear mechanism was abrasion, independently of the used lubricant. Adhesive wear was observed for the systems without mucin. Tribocorrosion activity and wear coefficient were lower in the presence of mucin. None of the studied artificial lubricants mimicked the effect of human saliva (HS) on the tribological behavior of the studied pair since this lubricant led to the lowest friction coefficient and highest corrosion activity.

An exploratory study of perfectionism, professional factors and psychological well-being of dentistry academics.

BACKGROUND: Well-being might be lower among dentistry professionals than other health professionals, and differ by personal, professional and sociodemographic factors. Few studies have considered dentistry academics who have different work roles and functions than clinicians. This exploratory study focused on well-being among dentistry academics and aimed to explore associations with perfectionism, professional factors and sociodemographics. METHOD: An online survey was carried out with academic staff in Dentistry and Oral Health departments of nine Universities in Australia and New Zealand. Well-being was assessed using the 22-item Psychological General Well-Being Index, with a maximum score of 110 indicating good well-being. Perfectionism was assessed using the 8-item Short Almost Perfect Scale, with a maximum score of 56 and a higher score indicating perfectionism. Twenty items were used to assess professional and 7 items assessed sociodemographic factors. Associations were explored using correlation and multiple linear regression. RESULTS: There was no significant bivariate association between perfectionism and well-being. Multiple linear regression indicated a significant association between hours of undergraduate teaching and psychological well-being, after adjustment for age, gender, income and overall health. CONCLUSION: This exploratory study showed poor well-being among dentistry academics, particularly in those teaching undergraduate students for more than 6 h/week.

Blockade of CD73 delays glioblastoma growth by modulating the immune environment.

Immunotherapy as an approach for cancer treatment is clinically promising. CD73, which is the enzyme that produces extracellular adenosine, favors cancer progression and protects the tumor from immune surveillance. While CD73 has recently been demonstrated to be a potential target for glioma treatment, its role in regulating the inflammatory tumor microenvironment has not yet been investigated. Thus, this study explores the immunotherapeutic value of the CD73 blockade in glioblastoma. The immuno-therapeutic value of the CD73 blockade was evaluated in vivo in immunocompetent pre-clinical glioblastoma model. As such, glioblastoma-bearing rats were nasally treated for 15 days with a siRNA CD73-loaded cationic-nanoemulsion (NE-siRNA CD73R). Apoptosis was determined by flow cytometry using Annexin-V staining and cell proliferation was analyzed by Ki67 expression by immunohistochemistry. The frequencies of the CD4+, CD8+, and CD4+CD25highCD39+ (Treg) T lymphocytes; CD11b+CD45high macrophages; CD11b+CD45low-microglia; and CD206+-M2-like phenotypes, along with expression levels of CD39 and CD73 in tumor and tumor-associated immune cells, were determined using flow cytometry, while inflammatory markers associated with tumor progression were evaluated using RT-qPCR. The CD73 blockade by NE-siRNA CD73 was found to induce tumor cell apoptosis. Meanwhile, the population of Tregs, microglia, and macrophages was significantly reduced in the tumor microenvironment, though IL-6, CCL17, and CCL22 increased. The treatment selectively decreased CD73 expression in the GB cells as well as in the tumor-associated-macrophages/microglia. This study indicates that CD73 knockdown using a nanotechnological approach to perform nasal delivery of siRNA-CD73 to CNS can potentially regulate the glioblastoma immune microenvironment and delay tumor growth by inducing apoptosis.

CD73 as a target to improve temozolomide chemotherapy effect in glioblastoma preclinical model.

Glioblastoma is the most devastating primary brain tumor and effective therapies are not available. Treatment is based on surgery followed by radio and chemotherapy with temozolomide (TMZ), but TMZ increases patient survival only by 2 months. CD73, an enzyme responsible for adenosine production, emerges as a target for glioblastoma treatment. Indeed, adenosine causes tumor-promoting actions and CD73 inhibition increases sensitivity to TMZ in vitro. Here, a cationic nanoemulsion to nasal delivery of siRNA CD73 (NE-siRNA CD73) aiming glioblastoma treatment was employed alone or in combination with TMZ. In vitro, two glioblastoma cell lines (C6 and U138MG) with a chemo-resistant profile were used. Treatment alone with NE-siRNA CD73 reduced C6 and U138MG glioma cell viability by 70% and 25%, respectively. On the other hand, when NE-siRNA + TMZ combined treatment was employed, a reduction of 85% and 33% of cell viability was observed. Notably, treatment with NE-siRNA CD73 of glioma-bearing Wistar rats reduced tumor size by 80%, 60% more than the standard chemotherapy with TMZ, but no synergistic or additive effect was observed in vivo. Additionally, NE-siRNA CD73, TMZ or combined therapy decreased adenosine levels in liquor confirming the importance of this nucleoside on in vivo GB growth. Finally, no hemolytic potential was observed. These results suggest that nasal administration of NE-siRNA CD73 exhibits higher antiglioma effect when compared to TMZ. However, no synergistic or additive in vivo was promoted by the therapeutic regimen employed in this study.

Nasal Administration of Cationic Nanoemulsions as CD73-siRNA Delivery System for Glioblastoma Treatment: a New Therapeutical Approach.

Glioblastoma is the most devastating primary brain tumor. Effective therapies are not available, mainly due to high tumor heterogeneity, chemoresistance, and the difficulties imposed by blood-brain barrier. CD73, an enzyme responsible for adenosine (ADO) production, is overexpressed in cancer cells and emerges as a target for glioblastoma treatment. Indeed, ADO causes a variety of tumor-promoting actions, particularly by inducing tumor immune escape, whereas CD73 inhibition impairs tumor progression. Here, a cationic nanoemulsion to deliver CD73siRNA (NE-siRNA CD73R) via nasal route aiming glioblastoma treatment was developed. NE-siRNA CD73R was uptaken by glioma cells in culture, resulting in a parallel 60-80% decrease in AMPase activity and 30-50% in cell viability. Upon nasal delivery, NE-siRNA CD73R was detected in rat brain and serum. Notably, treatment with CD73siRNA complexes of glioma-bearing Wistar rats reduced tumor growth by 60%. Additionally, NE-siRNA CD73R treatment decreased 95% ADO levels in liquor and tumor CD73 expression, confirming in vivo CD73 silencing. Finally, no toxicity was observed in either primary astrocytes or rats with this cationic nanoemulsion. These results suggest that nasal administration of cationic NE as CD73 siRNA delivery system represents a novel potential treatment for glioblastoma. Graphical Abstract Glioblastoma is the most common and devastating form of primary brain tumor. CD73, a protein involved in cell-cell adhesion and migration processes and also responsible for extracellular adenosine (ADO) production, is overexpressed by glioma cells and emerges as an important target for glioma treatment. Indeed, ADO participates in tumor immune escape, cell proliferation, and angiogenesis, and CD73 inhibition impairs those processes. Here, a cationic nanoemulsion to deliver CD73 siRNA (NE-siRNA CD73R) via nasal route aiming glioblastoma treatment was developed. NE-siRNA CD73R knockdown in vitro and in vivo CD73. Upon nasal delivery of NE-siRNA CD73R, the treatment markedly reduced tumor volume by 60% in a rat preclinical glioblastoma model. The treatment was well tolerated, and did not induce kidney, liver, lung, olfactory, bone marrow, or behavior alterations. These results indicate that the nasal administration of NE as a CD73 siRNA delivery system offered an efficient means of gene knockdown and may represent a potential alternative for glioblastoma treatment.

Adalimumab medium-term dosing strategy in moderate-to-severe hidradenitis suppurativa: integrated results from the phase III randomized placebo-controlled PIONEER trials.

BACKGROUND: Weekly adalimumab (Humira® ) is approved for the treatment of hidradenitis suppurativa (HS) based on the 12-week placebo-controlled periods of the two phase III PIONEER trials. OBJECTIVES: Using PIONEER integrated trial results, we aimed to evaluate the optimal medium-term adalimumab maintenance dosing strategy for moderate-to-severe HS. METHODS: Each trial had two double-blind periods; 12-week Period A and 24-week Period B. Patients randomized to adalimumab 40 mg every week (ADAew) (Period A), were rerandomized in Period B to ADAew (ADAew/ew), ADA every other week (ADAew/eow), or placebo (ADAew/pbo). Placebo-randomized patients were reassigned in Period B to ADAew (PIONEER I) or placebo (PIONEER II). The primary outcome was HS Clinical Response (HiSCR). Patients who lost response during Period B were discontinued from the study and offered an option to enter the open-label extension (OLE) to receive ADAew. Results are reported across the two study periods, and data were combined from the two study periods and the OLE. RESULTS: For week-12 HiSCR achievers, the HiSCR week-36 rate was 48·1% (ADAew/ew) vs. 46·2% (ADAew/eow) and 32·1% (ADAew/pbo). Combining (post hoc) these patients with week-12 partial responders further differentiated outcomes in Period B (ADAew/ew 55·7% vs. ADAew/eow 40·0% and ADAew/pbo 30·1%). Period-B adverse-event rates were ADAew/ew 59·6% vs. ADAew/eow 57·4% and ADAew/pbo 65·0%. One patient (ADAew/ew) reported a serious infection. CONCLUSIONS: Weekly adalimumab treatment, effective throughout 36 weeks, was the optimal maintenance medium-term dosing regimen for this population. At least partial response after 12 weeks with continued weekly dosing had better outcomes than dose reduction or interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy. No new safety risks were identified. What's already known about this topic? Hidradenitis suppurativa (HS) is a chronic inflammatory disease, commonly misinterpreted as an infection and treated with long-term antibiotic regimens or surgical incisions. Based on the chronicity of HS and the lack of evidence for efficacious and safe long-term HS treatments, it is important to evaluate medium- to long-term therapies for HS. Weekly adalimumab (Humira® ) is approved for the treatment of moderate-to-severe HS based on the two phase III PIONEER trials. What does this study add? This study pooled data from the two PIONEER trials, providing a more robust assessment of outcomes. After at least partial treatment success with weekly adalimumab short-term therapy (12 weeks), continuing weekly dosing during the subsequent 24 weeks had better outcomes than dose reduction or treatment interruption. Patients who do not show at least a partial response to weekly adalimumab by week 12 are unlikely to benefit from continued therapy.

CD73 Downregulation Decreases In Vitro and In Vivo Glioblastoma Growth.

Glioblastoma is the worst and most common primary brain tumor. Here, we demonstrated the role of CD73, an enzyme responsible for adenosine (ADO) production, in glioblastoma progression. ADO increased glioma cell viability via A1 receptor sensitization. CD73 downregulation decreased glioma cell migration and invasion by reducing metalloproteinase-2 and vimentin expression and reduced cell proliferation by 40%, which was related to necrosis and sub-G1 phase blockage of cell cycle. Those effects also involved the stimulation of Akt/NF-kB pathways. Additionally, CD73 knockdown or enzyme inhibition potentiated temozolomide cytotoxic effect on glioma cells by decreasing the IC50 value and sensitizing cells to a non-cytotoxic drug concentration. CD73 inhibition also decreased in vivo rat glioblastoma progression. Delivery of siRNA-CD73 or APCP reduced tumor size by 45 and 40%, respectively, when compared with control. This effect was followed by a parallel 95% reduction of ADO levels in cerebrospinal fluid, indicating the role of extracellular ADO in in vivo glioma growth. Treatment did not induce systemic damage or mortality. Altogether, we conclude that CD73 is an interesting target for glioblastoma treatment and its inhibition may provide new opportunities to improve the treatment of brain tumors. Graphical Abstract ᅟ.

Assessing epidemiology of leprosy and socio-economic distribution of cases.

Leprosy still represents a serious health problem in a number of countries, including Brazil. Although leprosy has been associated with poverty for a long time, it is still difficult to accurately define this relationship. Here, we evaluated in an endemic municipality the progress from 1995 to 2015 of epidemiological indicators to establish if there were any strong associations between social indicators and the occurrence of leprosy. An ecological study was conducted using the SINAN database (Brazilian leprosy-national notifiable diseases information system) in combination with georeferencing of leprosy cases. The georeferencing used the ArcGis programme and occurrence of cases was evaluated in relation to the Health Vulnerability Index (HVI), an indicator that categorises socio-economic and sanitation factors. The data identified a marked decrease in the overall prevalence of leprosy, a reduction in the new case-detection rate and a reduction in the number of cases with grade 2 disabilities (albeit with transient peaks in 2007 and 2015). Logistic regression analysis showed association of detection rates with elevated HVI. Thus, while the epidemiological indicators point to the elimination of leprosy, there is evidence of hidden cases and an association between higher rates of leprosy detection and greater social vulnerability remain.

Long-term optimization of outcomes with flexible adalimumab dosing in patients with moderate to severe plaque psoriasis.

BACKGROUND: The recently updated dosing recommendation for adalimumab for moderate to severe plaque psoriasis states that patients with inadequate response to adalimumab every other week (EOW) after 16 weeks may benefit from an increase in dosing frequency to 40 mg every week (EW). OBJECTIVE: To determine the long-term efficacy of adalimumab in patients with psoriasis with flexibility to escalate and de-escalate between EOW and EW dosing. METHODS: Data from an open-label study in patients with psoriasis who had received adalimumab in phase 2/3 studies and their extensions were included. Patients initially received 40 mg adalimumab EOW for 24 weeks. From weeks 24-252, patients whose Psoriasis Area and Severity Index response was <50% (PASI 50) could have their dose-escalated to 40 mg EW and were re-evaluated at 6 and 12 weeks and then every 12 weeks thereafter. Patients who had their dose-escalated and achieved a PASI 75 response were de-escalated to EOW and could re-escalate to EW if response fell below PASI 50 again; no further de-escalation was allowed. Changes in PASI scores were reported at the last visit before dose escalation or de-escalation. RESULTS: By week 24, 64.1% of patients in the overall population (n = 1256) achieved ≥PASI 75 response, 40.3% ≥PASI 90 response and 21.7% PASI 100 response. Patients who had a

Protocolo com nove dias de progesterona para inseminação artificial em tempo fixo em vacas taurinas adaptadas ao clima tropical / Protocol with nine days of progesterone for fixed-time artificial insemination in Bos taurus cows adapted to the tropical weather

Três experimentos foram realizados para adaptar um protocolo de sincronização de estro e da ovulação para ser utilizado em programas de inseminação artificial em tempo fixo (IATF) em vacas taurinas tropicalmente adaptadas. No Exp. 1 (crossover), vacas pluríparas Curraleiro Pé-Duro (n= 12) receberam um dispositivo intravaginal contendo 1g de P4 por oito dias e 2mg de BE intramuscular (IM) no momento da inserção do dispositivo (dia 0). No dia da remoção do dispositivo (dia 8), as fêmeas receberam 150µg de D-cloprostenol sódico e 300UI de gonadotrofina coriônica equina (eCG) IM, sendo, então, divididas aleatoriamente para receber 1mg de BE no dia 8 (BE8) ou 1mg de BE no dia 9 (BE9). A aplicação de BE no D9 atrasou a ovulação em aproximadamente 15 horas (P<0,05). No Experimento 2, foram avaliados protocolos com oito (P4D8) e nove dias (P4D9) de exposição à progesterona, resultando em parâmetros de desenvolvimento folicular e luteal semelhantes entre os tratamentos (P>0,05). No Experimento 3, os protocolos hormonais de IATF BE8 e P4D9 foram testados para a taxa de prenhez, alcançando 23% (10/43) e 20% (9/45), respectivamente (P>0,05). Embora o grupo P4D9 tenha mostrado avanço na proporção de animais que responderam ao protocolo quando comparado ao protocolo BE8, este não se refletiu em melhora na taxa de prenhez.(AU)

Three experiments were performed to adapt a synchronization protocol of estrus synchronization and ovulation to be used in fixed time artificial insemination programs (FTAI) in tropically adapted Bos taurus cows. In Exp. 1 (crossover) multiparous Curraleiro Pé-Duro cows (n= 12) received an intravaginal device containing 1g of P4 for 8 days and 2mg of EB at the time of device insertion (Day 0). On the P4 device removal (Day 8) females received 150g of D-cloprostenol Sodic and 300IU of equine chorionic gonadotropin (eCG). Then, they were randomly divided to receive 1mg of EB on Day 8 (EB8) or on Day 9 (EB9). EB9 delayed ovulation approximately 15 hours (P<0.05). In Exp. 2, protocols using progesterone for eight (P4D8) or nine days (P4D9) were evaluated, resulting in similar parameters of folicular and luteal development (P>0.05). In Exp. 3, EB8 and P4D9 protocols were used to evaluate the pregnancy rate, reaching 23% (10/43) and 20% (9/45), respectively (P>0.05). Although P4D9 protocol has shown improvement in proportion of animals that responded to the protocol when compared to EB8 protocol, it was not able to improve pregnancy rate.(AU)

Enhanced expression of PD-L1 and IFN-γ on dendritic cells is associated with BCG-induced Th2 inhibition.

Accumulating evidence indicates that the exposure to Mycobacterium bovis bacillus Calmette-Guérin (BCG) prevents the development of allergy and the airway dendritic cells (DCs) may be involved in this protective effect. However, studies to better characterize the specific interactions between BCG and DCs and their role in this mycobacteria-mediated Th2 cell suppression are still ongoing. This study aimed to evaluate the effect of the neonatal BCG vaccination in the innate immune response in a mouse model of ovalbumin (OVA)-induced airway inflammation. BCG treated neonatal BALB/c mice were sensitized and challenged with aerosolized OVA. Twenty-four hours after the last challenge, samples were collected for analysis. The intranasal BCG treatment inhibited the allergic Th2-response by decreasing the allergen-induced eosinophilic inflammation, EPO activity, CCL11, IL-25, TSLP, IL-4 and IL-5 lung levels, and serum levels of IgE. Mycobacteria treatment increased lung levels of IL-10 and TGF-ß, and the TLR2 and TLR4 expressions by pulmonary CD11c+CD103+CD8α+ DCs. Additionally an enhanced expression of PD-L1 was observed besides an increased production of IFN-γ by these cells. These results indicated that neonatal BCG vaccination inhibits key features of allergic airway inflammation, probably by promoting T regulatory immune response via an enhanced expression of TLR2, TLR4 and PD-L1 on DCs.

Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice.

Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge. Obesity induced an increase of inducible nitric oxide synthase (iNOS)-expressing macrophages and neutrophils which peaked at 48 h after the last OVA challenge, and was associated with higher levels of interleukin (IL)-4, IL-9, IL-17A, leptin and interferon (IFN)-γ in the lungs. Higher goblet cell hyperplasia was associated with elevated mast cell influx into the lungs and trachea in the obese allergic mice. In contrast, early eosinophil influx and lower levels of IL-25, thymic stromal lymphopoietin (TSLP), CCL11 and OVA-specific immunoglobulin (IgE) were observed in the obese allergic mice in comparison to non-obese allergic mice. Moreover, obese mice showed higher numbers of mast cells regardless of OVA challenge. These results indicate that obesity affects allergic airway inflammation through mechanisms involving mast cell influx and the release of TSLP and IL-25, which favoured a delayed immune response with an exacerbated Th1, Th2 and Th17 profile. In this scenario, an intense mixed inflammatory granulocyte influx, classically activated macrophage accumulation and intense mucus production may contribute to a refractory therapeutic response and exacerbate asthma severity.

Efficacy and safety of adalimumab in Chinese patients with moderate-to-severe plaque psoriasis: results from a phase 3, randomized, placebo-controlled, double-blind study.

BACKGROUND: This phase 3 trial is the first to evaluate the efficacy and safety of treatment with the systemic TNF-α inhibitor, adalimumab, for Chinese patients with moderate-to-severe plaque psoriasis. METHODS: In the 12-week, double-blind, placebo-controlled Period A, patients were randomized 4 : 1 to receive adalimumab 40 mg every-other-week (following a single 80 mg dose), or placebo every-other-week. In the subsequent 12-week, open-label, Period B, all patients received adalimumab 40 mg every-other-week starting at week 13, following a single, blinded dose at week 12 of adalimumab 80 mg or matching placebo (for patients receiving placebo or adalimumab in Period A respectively). In Period A, efficacy was analysed for all randomized patients and safety for all patients receiving ≥1 dose of the study drug. RESULTS: For the 425 patients in this study (87 placebo; 338 adalimumab), a higher percentage randomized to adalimumab achieved the primary endpoint of ≥75% improvement from baseline in PASI score (PASI 75) at week 12: placebo 11.5% (10/87); adalimumab 77.8% (263/338; P < 0.001). Physician's Global Assessment of clear to minimal was achieved at week 12 by 14.9% placebo (13/87) and 80.5% adalimumab (272/338; P < 0.001). For patients who received adalimumab at any time during the study (All-adalimumab Population), treatment-emergent adverse events (AEs) were reported by 63.4%; the most common was upper respiratory infection (16.1%). Serious AEs were reported by 3.5% of the All-adalimumab Population, and serious infectious AEs by 1.2%, which include lung infection, pneumonia and tuberculosis [2 (0.5%) patients each]. There was one death (chronic heart failure). CONCLUSION: In these Chinese patients with moderate-to-severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment.

Anxiety and Stress Levels on Liver Transplantation Candidates.

The objective of the present study was to determine the anxiety and stress levels of liver transplant candidates during the preoperative period. A cross-sectional, prospective study was conducted on 52 liver transplantation candidates seen at a specialized public hospital outpatient clinic in the interior of the state of São Paulo, Brazil. Data were collected from November 2014 to April 2015 using a self-applicable questionnaire for the assessment of anxiety (State-Trait Anxiety Inventory, short version) and stress (Perceived Stress Scale), in addition to sociodemographic and clinic characterization. The mean (±SD) anxiety level detected was 23.06 ± 5.51 points, with 1.92% of the subjects showing minimum levels (0 to 12 points), 59.62% a medium level (12 to 24 points), 36.54% a moderate level (24 to 36 points), and 1.92% a severe level (36 to 48 points) of anxiety. The mean level on the stress scale was 12.10 ± 5.62 points, with 7.69% of the subjects showing high stress levels. When individuals with good and poor stress levels were compared, a significant difference was observed between them (P = .0004). The Spearman correlation test showed that the higher the stress, the higher the levels of anxiety (r = 0.4258), P < .0001. The present study contributes to the analysis of the mental health of liver transplantation candidates in view of the need for interventions for the improvement of anxiety and stress levels since the waiting period for the organ generates emotional changes that can affect the quality of life of the patient and the success of this complex therapeutic modality.

Sleep Quality Assessment and Daytime Sleepiness of Liver Transplantation Candidates.

OBJECTIVE: The goal of this study was to evaluate the sleep quality and daytime sleepiness of patients eligible for liver transplants. METHODS: A cross-sectional prospective study was conducted on liver transplant candidates from a transplant center in the interior of São Paulo State. The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale questionnaires were applied to obtain demographic and clinical characteristics and to assess sleep quality and daytime sleepiness. RESULTS: The mean (±SD) score on the Epworth Sleepiness Scale of the 45 liver transplantation candidates was 7.00 ± 2.83 points, with 28.89% having scores >10 points, indicating excessive daytime sleepiness. The mean score on the Pittsburgh Sleep Quality Index was 6.64 ± 4.95 points, with 60% of the subjects showing impaired sleep quality, with scores >5 points. The average sleep duration was 07:16 h. Regarding sleep quality self-classification, 31.11% reported poor or very poor quality. It is noteworthy that 73.33% of patients had to go to the bathroom, 53.33% woke up in the middle of the night, and 40.00% reported pain related to sleeping difficulties. Comparison of subjects with good and poor sleep quality revealed a significant difference in time to sleep (P = .0002), sleep hours (P = .0003), and sleep quality self-classification (P = .000072). CONCLUSION: Liver transplant candidates have a compromised quality of sleep and excessive daytime sleepiness. In clinical practice, we recommend the evaluation and implementation of interventions aimed at improving the sleep and wakefulness cycle, contributing to a better quality of life.

Protective effect of a hydrogel containing Achyrocline satureioides extract-loaded nanoemulsion against UV-induced skin damage.

Achyrocline satureioides is a medicinal plant widely used in South America that exhibits a well-documented antioxidant activity. Such activity has been related to their main aglycone flavonoids quercetin, luteolin, and 3-O-methylquercetin (3MQ). This study addresses the development of antioxidant hydrogels containing an A. satureioides extract-loaded nanoemulsions aimed at topical application. The systems investigated were A. satureioides extract-loaded nanoemulsions (ASNE) obtained by spontaneous emulsification procedure formulated in semisolid hydrogels composed of Carbopol® Ultrez 20 (HASNE). Hydrogels exhibit a non-Newtonian pseudoplastic behavior. A higher release of 3MQ from ASNE (3.61µg/cm(2)/h) was observed when compared with HASNE (2.83µg/cm(2)/h). Different parameters that may have an influence on the retention of flavonoids into the skin were investigated by using a Franz-type diffusion cells. Indeed, the amount of formulation applied on donor compartment was found to play a crucial role. At the optimized conditions, retention of approximately 2µg/cm(2) of flavonoids was detected into the skin. A higher retention of 3MQ was detected (approximately 1.0µg/cm(2)) in comparison with the other flavonoids. Finally, a protection the porcine ear skin by formulations, against oxidative stress generated by UVA/UVB light was demonstrated by means of TBARS, protein carbonylation, and protein thiol content assays. The overall results showed the potential of the formulations developed in this study for the prevention of oxidative stress on the skin.

Assessing an imidazolium salt's performance as antifungal agent on a mouthwash formulation.

AIMS: This study demonstrates the development of a mouthwash formulation containing the imidazolium salt (IMS) 1-n-hexadecyl-3-methylimidazolium chloride (C16 MImCl), considering its stability and efficacy against Candida sp. Biofilm formation. METHODS AND RESULTS: A variety of in vitro test methods were applied, assessing contaminated acrylic resin strip specimens before and after applying the mouthwash formulations. The formulation using C16 MImCl presented a similar antibiofilm activity to cetylpyridinium chloride one and a commercial mouthwash, but at a 10 times lower concentration. Scanning electron microscopy imaging demonstrated that the selected mouthwash preparation fully destroys the biofilm cells, while with the hypoallergenicity test no irritant effect was observed in ex vivo model. CONCLUSIONS: The results presented herein indicate a high potential for imidazolium salts application as mouthwash agents that can eliminate Candida biofilm growth at very low concentrations. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates a new and effective antibiofilm formulation containing the IMS C16 MImCl. These findings suggest the IMS' use as mouthwash formulations active ingredient against Candida biofilms on oral surfaces, as it outperforms the often used cetylpyridinium chloride at a 10 times lower concentration.

In Vitro Evaluation of Mucosa Permeation/Retention and Antiherpes Activity of Genistein from Cationic Nanoemulsions.

In this report, we described the genistein distribution on excised porcine esophageal mucosa from cationic nanoemulsions, as well as the anti-HSV-1 activity against a viral strain resistant to acyclovir. Genistein-loaded cationic nanoemulsions were prepared by spontaneous emulsification. This procedure yielded monodisperse nanoemulsions exhibiting a mean droplet size of approximately 200-300 nm. Hydroxyethyl cellulose (HEC) was added at the end of the manufacturing process as a thickening agent (at 3%). Such formulations exhibit a non-Newtonian pseudoplastic behavior. The addition of HEC significantly reduces the genistein flux through excised porcine mucosa specimens as compared with values elicited by nanoemulsions before thickening. Furthermore, a significant increase of genistein retention in mucosa was observed as compared to the genistein propylene glycol solution, as illustrated by confocal fluorescence microscopy images. Formulations exhibited antiherpetic activity in vitro against HSV-1 (strain 29R). Taken together, these results suggest that these formulations have promising potential to be used topically for herpes infections.

HiSCR (Hidradenitis Suppurativa Clinical Response): a novel clinical endpoint to evaluate therapeutic outcomes in patients with hidradenitis suppurativa from the placebo-controlled portion of a phase 2 adalimumab study.

BACKGROUND: Determining treatment response for patients with hidradenitis suppurativa (HS) can be challenging due to limitations of current disease activity evaluations. OBJECTIVE: Evaluate the novel, validated endpoint, Hidradenitis Suppurativa Clinical Response (HiSCR) and its utility as an outcome measure. METHODS: Patients with baseline total abscess and inflammatory nodule count (AN count) of at least three and draining fistula count of 20 or fewer comprised the post hoc subpopulation analysed. HiSCR (at least a 50% reduction in total AN count, with no increase in abscess count, and no increase in draining fistula count relative to baseline) and HS-PGA Response [Hidradenitis Suppurativa-Physician's Global Assessment score of clear, minimal, or mild, with at least a 2-grade improvement from baseline] were used to evaluate patient response after adalimumab treatment weekly, every other week, or placebo (1 : 1 : 1). RESULTS: The subpopulation included 132 (85.7%) patients; 70.5% women and 73.5% white. At week 16, HiSCR was achieved by 54.5% receiving weekly adalimumab, 33.3% every other week, and 25.6% placebo and HS-PGA Response was achieved by 20.5% receiving weekly adalimumab, 6.7% every other week and 2.3% placebo. CONCLUSION: HiSCR was more responsive to change than HS-PGA Response in this subpopulation.