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Paula dos Passos Menezes,1 Luiza Abrahão Frank,2 Bruno dos Santos Lima,1 Yasmim Maria Barbosa Gomes de Carvalho,1 Mairim Russo Serafini,1 Lucindo José Quintans-Júnior,3 Adriana Raffin Pohlmann,4 Sílvia Stanisçuaski Guterres,2 Adriano Antunes de Souza Araújo1 1Department of Pharmacy, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; 2College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; 3Department of Physiology, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil; 4Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil Abstract: Chronic venous insufficiency is characterized by chronic reflux disorder of blood from the peripheral to the central vein, with subsequent venous hypertension and resulting changes in the skin. Traditionally, nonsurgical treatments relied on the use of compression therapy, and more recently a variety of flavonoids have been shown to have positive effects. There have also been developments of more effective drug delivery systems using various textiles and nanotechnology to provide new therapeutic options. Our objective was to use nanotechnology to develop a new formulation containing hesperetin (Hst), a substance not previously used in the treatment of chronic venous insufficiency, impregnated into textile fibers as a possible alternative treatment of venous diseases. We prepared the nanocapsules using the interfacial deposition of preformed polymer method with an Hst concentration of 0.5 mg/mL and then characterized the size and distribution of particles. To quantify the Hst in the samples, we developed an analytical method using high-performance liquid chromatography. Studies of encapsulation efficiency (98.81%±0.28%), microscopy, drug release (free-Hst: 104.96%±12.83%; lipid-core nanocapsule-Hst: 69.90%±1.33%), penetration/permeation, drug content (0.46±0.01 mg/mL) and the effect of washing the textile after drug impregnation were performed as part of the study. The results showed that nanoparticles of a suitable size and distribution with controlled release of the drug and penetration/permeation into the skin layers were achieved. Furthermore, it was established that polyamide was able to hold more of the drug, with a 2.54 times higher content than the cotton fiber; after one wash and after five washes, this relation was 2.80 times higher. In conclusion, this is a promising therapeutic alternative to be further studied in clinical trials. Keywords: lipid-core nanocapsules, polymer, hesperetin, fabrics, impregnation, medical textiles, polyamide, poly(ε-caprolactone)

We report superconductivity at TC ∼3.8 K in the new ternary phase Ta5GeB2. Bulk superconductivity is confirmed by magnetization, electrical resistivity and heat capacity measurements, the results showing conventional bulk superconductivity. Ta5GeB2 is a further example of a stoichiometric T2 phase with Cr5B3 prototype structure.

In this work, we report superconductivity in the new ternary Ta1-xHfxB system. We also show clearly evidence that appropriate amounts of Hf substitution at the Ta site induce the stabilization of the orthorhombic FeB prototype structure in this system. Bulk superconductivity is confirmed by magnetization, electronic transport and specific heat measurements. The Hall signal has temperature dependence and the specific heat data at low temperature deviate from the conventional exponential temperature dependence in Ta0.7Hf0.3B. These results suggest multiband superconductivity in this compound.

In this work, we report superconductivity in the new ternary Ta1-xHfxB system. We also show clearly evidence that appropriate amounts of Hf substitution at the Ta site induce the stabilization of the orthorhombic FeB prototype structure in this system. Bulk superconductivity is confirmed by magnetization, electronic transport and specific heat measurements. The Hall signal has temperature dependence and the specific heat data at low temperature deviate from the conventional exponential temperature dependence in Ta0.7Hf0.3B. These results suggest multiband superconductivity in this compound.

We report bulk superconductivity in ZrVGe withTc=6K determined by magnetization, electronic transport and specific heat measurements. From the analysis of magnetization and resistivity data we obtain the thermodynamic critical fieldsμ0Hc1andμ0Hc2, respectively. The heat capacity data deviate from conventional BCS theory suggesting possible unconventional superconducting behavior.

Category: Ankle Introduction/Purpose: Ankle fractures are a common cause of functional mobility that have seen a dramatic rise incidence over the past decade1. The purpose of this study was to compare the outcomes and prognosis of various fracture sub-types by utilizing two validated patient reported outcome measures: the PROMIS Physical Function and Pain Interference Computer Adaptive Tests (CATs) for patients at a major tertiary facility and level I trauma center. Methods: 12-month post-operative PROMIS Physical Function and Pain Interference CATs were collected for 125 ankle fracture patients presenting between 2014 and 2017. Patients were initially stratified by ankle fracture sub-type after examining pre- operative X-rays and further refined by the presence or absence of concomitant deltoid injury or posterior malleolar fracture. Patients defined as members of vulnerable populations and patients presenting more than 2 weeks from time of injury/with prior acute ipsilateral fracture were excluded. The distribution of PROMIS physical function and pain interference T-scores were assessed via a Shapiro-Wilk test and a one-way ANOVA was used for further evaluation. If significant differences were found between groups, pair-wise comparisons were tested via Dwass, Steel, Critchlow-Fligner multiple comparison analysis. Results: Fracture types and corresponding n-value in this study: (44) isolated lateral malleolar, (12) isolated medial malleolar, (12) bimalleolar, (44) trimalleolar, (6) isolated syndesmotic injury, and (8) isolated posterior malleolar fractures. Mean values for the PROMIS physical function and pain interference domains for each fracture sub-type were calculated and compared to reference population mean T-scores of 50 (SD = 10): isolated lateral malleolar (PF:50/PI:51), isolated medial malleolar (PF:52/PI:49), bimalleolar (PF:48/PI:50), trimalleoar (PF:47/PI:51), isolated posterior malleolar (PF:53/PI:44), and isolated syndesmotic injury (PF:60/PI:46). The Shapiro-Wilk test indicated a non-normal distribution for the post-operative PROMIS physical function T-scores across all fracture patients (p-value = 0.0421). Pair-wise comparisons were done to compare relative prognosis between fracture sub-types but failed to yield statistically significant differences in physical function or pain domains. Conclusion: Surgical intervention is effective in returning patients to normal levels of physical function and pain interference across all sub-types according to post-op T-scores. Although our analysis indicated a significant difference when comparing across all fracture sub-types, none of the pairwise sub-type comparisons showed statistical significance. Analyses of fracture sub-types determined trimalleolar injuries report the poorest outcomes for both PROMIS domains while the isolated syndesmotic and posterior malleolar groups reported the best outcomes. Further investigation with a larger sample size for each group is needed to delineate whether a significant difference exists for PROMIS physical function and pain interference scores.

Category: Sports, Achilles Tendon Introduction/Purpose: Achilles tendon rupture is a common injury with increasing incidence in adults. While multiple studies have been conducted to determine the optimal surgery for an Achilles rupture, there is a lack of consensus around which surgical method serves as the best treatment. The predominant surgical options that are currently performed include open repair and minimally invasive or percutaneous Achilles rupture surgery (PARS), with comparative studies between open and PARS showing similar functional results. However, there is a lack of objective patient reported outcomes (PRO) for these procedures in the literature. To our knowledge, our study is the first prospective study to use validated patient reported outcomes (PROMIS®) to compare pre-operative and post- operative outcomes for the PARS surgery. Methods: Pre- and post-operative data for the PROMIS Physical Function and Pain Interference Computer Adaptive Tests (CATs) was collected for over 100 Achilles rupture patients at a major tertiary care facility and level I trauma center starting in 2014. Each of these patients were contacted at regular intervals for repeat survey evaluation at multiple post-operative time points via email or phone. Patients treated for chronic Achilles rupture as well as patients without adequate post- operative follow up of a minimum of 2 years were excluded. We conducted a preliminary analysis on a total of 21 patients with acute Achilles rupture Injury treated with PARS and 2 years post- operative PROMIS follow up. For each outcome, a Wilcoxon signed-rank test was used to assess the mean difference between pre-operative and post-operative scores. The statistical analysis was conducted by statisticians who were blinded and worked independently of the orthopedics department. Results: Based on the Wilcoxon signed-rank test, there was significant mean difference between pre-op and post-op physical function scores (p=0.0009 < 0.05) and no significant mean difference between pre-op and post-op pain scores (p=0.1743 > 0.05). Mean post-operative scores were at the 54th percentile for function and 44th percentile for pain. Conclusion: While our study is a preliminary investigation into the use patient-reported outcomes in determining the outcomes of PARS, we aim to expand on our findings as more patients reach 2-year post- operative status. Our preliminary findings are however consistent with the literature regarding the viability of PARS in treating acute Achilles ruptures with positive results similar to other techniques. While patients’ experience a minor loss in post-operative physical function as compared to their pre- injury status, PARS restores physical function scores to that of the mean population while restoring pain scores to baseline levels.

Objective: The coronavirus disease 2019 pandemic has affected healthcare systems around the globe and massively impacted patients with various non-infectious, life-threatening conditions. Stroke is a major neurological disease contributing to death and disability worldwide, and is still an ongoing issue during the pandemic. Here we investigate the impact of the coronavirus disease 2019 outbreak on stroke manifestations, treatment courses, the outcome of stroke patients, and the hospitalization rate in a referral center for stroke management in Tehran, Iran. Methods: We extracted data regarding 31 stroke patients (10 patients with laboratory-confirmed coronavirus disease 2019) and compared the demographic and pathological characteristics of the patients with or without coronavirus disease 2019 infection. The association of demographic/pathological characteristics of stroke patients during the coronavirus disease 2019 pandemic and a corresponding period during the previous year (49 patients) and an earlier period during the same year as the pandemic (50 patients) was also evaluated. Results: The absolute number of admissions decreased about 40% during the coronavirus disease 2019 pandemic. Except for the stroke severity (P = 0.002), there were no significant changes in the demographic and pathological characteristics of the stroke patients during the three studied periods. A significantly higher mean of age (75.60 ± 9.54 versus 60.86 ± 18.45; P = 0.007), a significant difference in the type of stroke (P = 0.046), and significantly higher stroke severity (P = 0.024) were observed in stroke patients with coronavirus disease 2019 compared with those of stroke patients without coronavirus disease 2019. Treatment approaches, duration of hospitalization, and mortality rates did not differ significantly. Conclusions: This report shows that the pandemic caused the number of acute stroke admissions to plummet compared to other periods. Although the pandemic did not affect the treatment plans and care of the patients, stroke cases with coronavirus disease 2019 had higher age, more large vessel ischemic stroke, and more severe stroke. Further studies are urgently needed to realize the probable interaction of the coronavirus disease 2019 pandemic and the neurologic disease. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to test the reliability and structural validity (also called dimensionality) of the online Pittsburgh Sleep Quality Index among college students from low-income regions., Methods: We assessed 195 Brazilian college students from a low-income region (Gini index of 0.56), of whom 117 were reassessed to evaluate the reliability. We collected all data in a self-reported online twice, 2-week apart. We evaluated reliability and structural validity., Results: All questionnaire components showed reliability, correlation coefficient ≥0.49. In the structural validity, the confirmatory analysis showed better global model adjustment for the one-factor (RMSEA = 0.019; SRMR = 0.041; CFI = 0.992; TLI = 0.986) solution compared with two-factor (RMSEA = 0.099; SRMR = 0.070; CFI = 0.764; TLI = 0.619) and three-factor (RMSEA = 0.108; SRMR = 0.066; CFI = 0.763; TLI = 0.548) solutions, respectively., Discussion: The online questionnaire presents acceptable reliability and structural validity in Brazilian low-income regions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 De Moraes, Conceição da Silva, Lima, Marin, Hunt and Nascimento-Ferreira.)

The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC). The activity profile on membrane proteins involved in chemoresistance and tumorigenic signaling proteins was also evaluated. Among the compounds tested, the compounds 4c and 4a stood out with IC 50 values of 1.23 and 1.39 μM, respectively, against the MDA-MB-231 cell line. Both compounds exhibited IC 50 values of 0.45 μM for the MCF-7 cell line. Compounds 4a and 4c significantly decreased P-gp mRNA expression levels in MCF-7, 4 and 2 folds respectively. Regarding the impact on tumorigenic signaling proteins, compound 4a inhibited Akt2 in MDA-MB-231 and compound 4c inhibited the mRNA expression of VIM in MCF-7., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Anacardium occidentale L. stem bark Traditional Herbal Preparations (AoBTHPs) are widely used in traditional medicine to treat inflammatory conditions, such as diabetes. The present study aims to evaluate the anti-inflammatory, antioxidant, and genotoxic potential of red and white Portuguese AoBTHPs. Using a carrageenan-induced rat paw edema model, a significant anti-edema effect was observed for all tested doses of white AoBTHP (40.2, 71.5, and 127.0 mg/kg) and the two highest doses of red AoB THP (71.5 and 127.0 mg/kg). The anti-edema effect of red AoBTHP's highest dose was much more effective than indomethacin 10 mg/kg, Trolox 30 mg/kg, and Tempol 30 mg/kg. In DPPH, FRAP, and TAC using the phosphomolybdenum method, both types of AoBTHPs showed similar antioxidant activity and no genotoxicity up to 5000 µg/plate in the Ames test. The LC-UV/DAD-ESI/MS fingerprint allowed the identification of gallic and protocatechuic acids as the two main marker compounds and the presence of catechin, epicatechin, epigallocatechin gallate, and ellagic acid in both AoBTHPs. The obtained results support the validation of red and white AoB and their THPs as anti-inflammatory agents and contribute to the possible development of promising new therapeutic options to treat inflammatory conditions.

Root tubers of Asphodelus bento-rainhae subsp. bento-rainhae (AbR), a vulnerable endemic species, and Asphodelus macrocarpus subsp. macrocarpus (AmR) have traditionally been used in Portugal to treat inflammatory and infectious skin disorders. The present study aims to evaluate the in vitro antimicrobial activity of crude 70% and 96% hydroethanolic extracts of both medicinal plants, specifically against multidrug-resistant skin-related pathogens, to identify the involved marker secondary metabolites and also to assess the pre-clinical toxicity of these medicinal plant extracts. Bioguided fractionation of the 70% hydroethanolic extracts of both species using solvents of increasing polarity, namely diethyl ether (DEE: AbR-1, AmR-1), ethyl acetate (AbR-2, AmR-2) and aqueous (AbR-3, AmR-3) fractions, enabled the identification of the DEE fractions as the most active against all the tested Gram-positive microorganisms (MIC: 16 to 1000 µg/mL). Furthermore, phytochemical analyses using TLC and LC-UV/DAD-ESI/MS techniques revealed the presence of anthracene derivatives as the main constituents of DEE fractions, and five known compounds, namely 7'-(chrysophanol-4-yl)-chrysophanol-10'- C -beta- D -xylopyranosyl-anthrone ( p ), 10,7'-bichrysophanol ( q ), chrysophanol ( r ), 10-(chrysophanol-7'-yl)-10-hydroxychrysophanol-9-anthrone ( s ) and asphodelin ( t ) , were identified as the main marker compounds. All these compounds showed high antimicrobial activity, particularly against Staphylococcus epidermidis (MIC: 3.2 to 100 µg/mL). Importantly, no cytotoxicity against HepG2 and HaCaT cells (up to 125 µg/mL) for crude extracts of both species and genotoxicity (up to 5000 µg/mL, with and without metabolic activation) for AbR 96% hydroethanolic extract was detected using the MTT and Ames tests, respectively. Overall, the obtained results contribute to the concrete validation of the use of these medicinal plants as potential sources of antimicrobial agents in the treatment of skin diseases.

Dried leaves of Lannea velutina A. Rich. and Sorindeia juglandifolia (A. Rich.) Planch. ex Oliv. (family Anacardiaceae) are used in African traditional medicine. Although these medicinal plants have widespread use in the treatment of inflammatory diseases, there is no scientific data concerning their preclinical or clinical safety. This work aimed to investigate the phytochemical properties of the leaves of both species using HPLC-UV/DAD, as well as the in vivo oral repeated-dose toxicity of 70% hydroethanolic leaf extract of S. juglandifolia and the in vitro genotoxicity of 70% hydroethanolic leaf extracts of L. velutina and S. juglandifolia . Clinical signs of toxicity, body weight variations, and changes in food consumption, mortality, and blood biochemical parameters were monitored. Genotoxicity was assessed using the bacterial reverse mutation assay (Ames test) with and without metabolic activation, according to OECD guidelines. The obtained results showed the presence of gallic acid and anacardic acid as the main marker constituents in both species. No significant changes in general body weight or food intake were observed; small significant changes with no critical relevance were observed in the blood biochemistry of animals treated with S. juglandifolia hydroethanolic extract (50, 400, and 1000 mg/kg body weight) compared to those in the control group. No genotoxicity was observed in the bacterial reverse mutation assay with S. juglandifolia and L. velutina extracts (up to 5 mg/plate). The safety data obtained in vivo and lack of genotoxic potential in vitro points to the safe medicinal use of S. juglandifolia and L. velutina extracts.

Anacardium occidentale L. is used throughout the world to treat type 2 diabetes. In Portugal, a traditional herbal preparation made with stem bark of this species (AoBTHP) has been used for more than 30 years to treat this pathology. The AoBTHP was standardized on total phenolic content, and its hypoglycemic activity was assessed using db/db mice ( n = 26) for 92 days. Three doses (40.2, 71.5, and 127.0 mg/kg/day, per os ) were tested, and glibenclamide (5 mg/kg/day) was used as positive control. During the study, glycemia was measured under non-fasting or fasting states. In sequence, thin-layer chromatography bioautographic assays were used for the detection of possible alpha- and beta-glucosidase inhibitors. A significant hypoglycemic effect in fasting glycemia in days 31 and 57 was observed with the three tested doses. The 71.5 mg/kg and 127.0 mg/kg AoBTHPs significantly reduced non-fasting glycemia on day 24. The highest dose showed the most significant hypoglycemic effect. Gallic acid was identified as the major alpha- and beta-glucosidase inhibitor. The 127 mg/kg/day AoBTHP dose showed a greater glucose-lowering effect than glibenclamide. For the first time, a standardized AoBTHP was tested using an in vivo diabetes model, and its usage was preclinically validated for type 2 diabetes treatment. The hypoglycemic activity of an AoBTHP can be related to the presence of alpha- and beta-glucosidase inhibitors, such as gallic acid, but other mechanisms can also be involved.

Ischemic stroke is a common disease worldwide and leads to a significant rate of mortality and disability in patients every year, and imposes high costs on the health care system. The aim of this study was to evaluate the efficacy of the invasive method of mechanical thrombectomy for rapid intervention in ischemic stroke patients with large vessel involvement. Patients suspected of having a stroke, who were referred to Imam Hossein Hospital, were examined, and the diagnosis of stroke was confirmed. In the next stage, patients' MRS index was measured and the possibility of emergency thrombectomy was evaluated in patients. Patients who underwent thrombectomy were considered as the case group and the other patients were contemplated as the control group; then, the cases of the two groups were evaluated and compared. The mean age of patients was 66.63 ± 12.26 years. the use of emergency thrombectomy in the study group significantly reduced the MRS index of patients after 90 days (p <0.001), while a significant increase in the mean scores of the MRS index was seen in patients receiving pharmacological treatments. Also, there was no significant difference in terms of gender between the group of patients undergoing thrombectomy and the group receiving other treatments (p = 0.375). Emergency mechanical thrombectomy significantly reduces disability in stroke patients in the long term and can be a good alternative to conventional drug treatments.

The aim of this study was to investigate certain parameters regarding the maternal-fetal outcomes in a diet-induced obesity model. Obese, glucose-intolerant females who were exposed to a high-fat diet prior to pregnancy had lower placental efficiency and lower birth weight pups compared to the controls. Simple linear regression analyses showed that maternal obesity disrupts the proportionality between maternal and fetal outcomes during pregnancy. Maternal obesity is correlated with fetal outcomes, perhaps because of problems with hormonal signaling and exacerbation of inflammation in the maternal metabolic environment. The maternal obese phenotype altered the thickness of the placental layer, the transport of fatty acids, and the expression of growth factors. For example, lower expression of epidermal growth factor receptor (EGFR) mRNA in the obesity-prone group may have contributed to the rupture of the placental layers, leading to adverse fetal outcomes. Furthermore, maintenance of maternal glucose homeostasis and overexpression of placental growth factor (PGF) in the obesity-resistant group likely protected the placenta and fetuses from morphological and functional damage., (Published by Elsevier Inc.)

The use of natural products in sunscreen formulations as a prophylactic measure against skin cancer is receiving special attention attributed to the photoprotective and antioxidant properties of their chemical components. In this work, we describe the development of topical hydrogel formulations containing hydroalcoholic extract of red propolis (HERP), and the evaluation of the dermal sensitizing effect of the developed products. Sunscreen formulations composed of HERP in different concentrations (1.5, 2.5 or 3.5% w/w) alone or in combination with a chemical (octyl methoxycinnamate) and/or physical (titanium dioxide) filters were developed using poloxamer 407 as gel basis. The preliminary and accelerated stability tests, texture analysis and spreadability tests were performed. All formulations revealed to be stable in preliminary stability assessment. The formulations containing HERP 1.5 and 2.5% alone or associated with the filters showed intense modifications during accelerated stability test, which were confirmed by rheological analyses. The incorporation of HERP and filters in the poloxamer hydrogel decreased the toughness of product (p < 0.05) and the formulation containing HERP alone presented the lowest adhesivity (p < 0.001). The incorporation of HERP in the hydrogel decreased the poloxamer transition temperature, showing different rheological behavior with the increase of HERP concentration. The developed formulations were stable, exhibited non-Newtonian and pseudoplastic behavior, showing in vivo skin compatibility and no skin irritancy., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors.)

Spinal Cord Injury (SCI) promotes a cascade of inflammatory events that are responsible for neuronal death and glial scar formation at the site of the injury, hindering tissue neuroregeneration. Among the main approaches for the treatment of SCI, the use of biomaterials, especially gelatin methacryloyl (GelMA), has been proposed because it is biocompatible, has excellent mechanical properties, favoring cell adhesion and proliferation. In addition, it can act as a carrier of anti-inflammatory drugs, preventing the formation of glial scars. The present work presents the development and in situ application of a light-curing formulation based on GelMA containing a natural extract rich in anti-inflammatory, antioxidant and neuroprotective substances (hydroalcoholic extract of red propolis-HERP) in an experimental model of SCI in rats. The formulations were prepared and characterized by time of UV exposition, FTIR, swelling and degradation. The hydrogels containing 1 mg/mL of HERP were obtained by the exposure to UV radiation of 2 μL of the formulation for 60 s. The locomotor evaluation of the animals was performed by the scale (BBB) and demonstrated that after 3 and 7 days of the injury, the GelMA-HERP group (BBB = 5 and 7) presented greater recovery compared to the GelMA group (BBB = 4 and 5). Regarding the inflammatory process, using histomorphological techniques, there was an inflammation reduction in the groups treated with GelMA and GelMA-HERP, with decreases of cavitation in the injury site. Therefore, it is possible to conclude that the use of GelMA and GelMA-HERP hydrogel formulations is a promising strategy for the treatment of SCI when applied in situ, as soon as possible after the injury, improving the clinical and inflammatory conditions of the treated animals.

The Sphenophorus levis (Coleoptera, Curculionidae) is one of the main pests of sugarcane in Brazil. Although its major digestive proteases are known, its complex digestive process still needs to be further understood. We constructed a transcriptome from the midgut of 30-day-old larvae and identified sequences similar to its major digestive protease (cysteine cathepsin Sl-CathL), however, they presented a different amino acid than cysteine in the active cleft. We identified, recombinantly produced, and characterized Sl-CathL-CS, a pseudo cysteine protease, and verified that higher gene expression levels of Sl-CathL-CS occur in the midgut of 30-day old larvae. We reverted the serine residue to cysteine and compared the activity of the mutant (Sl-CathL-mutSC) with Sl-CathL-CS. Sl-CathL-CS presented no protease activity, but Sl-CathL-mutSC hydrolyzed Z-Phe-Arg-AMC (V max = 1017.60 ± 135.55, K m = 10.77 mM) and was inhibited by a cysteine protease inhibitor E-64 (K i = 38.52 ± 1.20 μM), but not by the serine protease inhibitor PMSF. Additionally, Sl-CathL-CS interacted with a sugarcane cystatin, while Sl-CathL-mutSC presented weaker interaction. Finally, protein ligand docking reinforced the differences in the catalytic sites of native and mutant proteins. These results indicate that Sl-CathL-CS is a pseudo-cysteine protease that assists protein digestion possibly by interacting with canecystatins, allowing the true proteases to work.

Complex regional pain syndrome type 1 (CRPS-1) is a painful syndrome without effective treatment. In order to explore possible new treatments, we used an animal model of CRPS-1 to examine the effects of β-Citronellol (βCT), a monoterpene found in a variety of plants that has been shown to have analgesic effects. We aimed to assess its effects alone, and complexed with β-cyclodextrin (βCD), which has been previously used to enhance the effects of a number of medicines. The βCT-βCD was characterized physiochemically using high performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC) and shown to have 80% efficiency. In the animal model, Swiss mice were treated with βCT, βCT-βCD, vehicle, pregabalin or sham and evaluated for hyperalgesia and motor coordination. Inflammatory mediators were measured by Western blot or ELISA and the descending pain pathway by immunofluorescence. βCT was shown to have an anti-hyperalgesic effect (without affecting motor coordination) that reduced inflammatory mediators and activated the descending pain pathway, and these effects were increased with complexation in βCD. Our results showed βCT-βCD to be a promising treatment for CRPS-1., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Previous data showed hypertensive rats subjected to chronic intracerebroventricular (ICV) infusion of angiotensin-(1-7) presented attenuation of arterial hypertension, improvement of baroreflex sensitivity, restoration of cardiac autonomic balance and a shift of cardiac renin-angiotensin system (RAS) balance toward Ang-(1-7)/Mas receptor. In the present study, we investigated putative central mechanisms related to the antihypertensive effect induced by ICV Ang-(1-7), including inflammatory mediators and the expression/activity of the RAS components in hypertensive rats. Furthermore, we performed a proteomic analysis to evaluate differentially regulated proteins in the hypothalamus of these animals. For this, Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats (TG) were subjected to 14 days of ICV infusion with Ang-(1-7) (200 ng/h) or 0.9% sterile saline (0.5 μl/h) through osmotic mini-pumps. We observed that Ang-(1-7) treatment modulated inflammatory cytokines by decreasing TNF-α levels while increasing the anti-inflammatory IL-10. Moreover, we showed a reduction in ACE activity and gene expression of AT1 receptor and iNOS. Finally, our proteomic evaluation suggested an anti-inflammatory mechanism of Ang-(1-7) toward the ROS modulators Uchl1 and Prdx1., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kangussu, Melo-Braga, de Souza Lima, Santos, de Andrade and Campagnole-Santos.)

Backgrounds: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death., Methods: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements., Results: We included 873 participants. Of eligible cases, 122 individuals (13.97%) died during hospitalization. The most common non-neurological manifestations were fever (81.1%), cough (76.1%), fatigue (36.1%), and shortness of breath (27.6%). Aging, male gender, co-morbidity, smoking, hemoptysis, chest tightness, and shortness of breath were associated with increased odds of severe cases and/or mortality. There were 561 (64.3%) cases with smell and taste dysfunctions (hyposmia: 58.6%; anosmia: 41.4%; dysguesia: 100%). They were more common among females (69.7%) and non-smokers (66.7%). Hyposmia/anosmia and dysgeusia were found to be associated with reduced odds of severe cases and mortality. Myalgia (24.8%), headaches (12.6%), and dizziness (11.9%) were other common neurological symptoms. Headaches had negative correlation with severity and death due to COVID-19 but myalgia and dizziness were not associated. The cerebrovascular events (n = 10) and status epilepticus (n = 1) were other neurological findings. The partial or full recovery of smell and taste dysfunctions was found in 95.2% after 8 weeks and 97.3% after 16 weeks. The parosmia (30.9%) and phantosmia (9.0%) were also reported during 8 weeks of follow-up. Five cases with mild headaches and 5 cases with myalgia were reported after 16 weeks of discharge. The demyelinating myelitis (n = 1) and Guillain-Barré syndrome (n = 1) were also found during follow-up., Conclusion: Neurological symptoms were found to be prevalent among individuals with COVID-19 disease and should not be under-estimated during the current pandemic outbreak.

Annona muricata L. is used in folk medicine for treatment of diseases related to inflammatory and oxidative processes. This study investigated the effect of the aqueous extract of A. muricata leaves (AEAM) on TPA-induced ear inflammation and antioxidant capacity, both in vitro and in vivo. The in vitro antioxidant capacity of AEAM was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing/antioxidant power (FRAP) and lipoperoxidation assays. Cytotoxicity and reactive oxygen species (ROS) release were evaluated in the L929 fibroblasts. Swiss mice were submitted to TPA application and were topically treated with AEAM (0.3, 1 or 3 mg/ear). After 6 h, inflammatory and oxidative parameters were evaluated. Quercetin 3-glucoside, rutin, chlorogenic acid, catechin and gallic acid were identified in AEAM. It also presented antioxidant activity in all in vitro assays used. Incubation with AEAM did not cause cell cytotoxicity but reduced ROS release from fibroblasts. Compared with the control group, treatment with AEAM significantly reduced ear oedema and mieloperoxidase activity in inflamed ears, as well as histological parameters of inflammation. These results were associated with the reduction of total hydroperoxides and modulation of catalase, but not superoxide dismutase activity. These findings show the anti-inflammatory effect of AEAM is associated with antioxidant capacity.

The COVID-19 pandemic has infected more than 22 million people worldwide. Although much has been learned about COVID-19, we do not know much about its neurological features and their outcome. This observational study was conducted on the patients of Imam Hossein Hospital, and 361 adult patients (214 males) with confirmed diagnosis of COVID-19 from March 5, 2020 to April 3, 2020, were enrolled. Data was gathered on age, sex, comorbidities, initial symptoms, symptoms during the disease course, neurological symptoms, and outcome. The mean age of the patients was 61.90 ± 16.76 years. The most common initial symptoms were cough, fever, and dyspnea. In 21 patients (5.8%), the initial symptom was neurological. History of dementia was associated with severe COVID-19 disease (odds ratio = 1.28). During the course of the disease, 186 patients (51.52%) had at least one neurological symptom, the most common being headache (109 [30.2%]), followed by anosmia/ageusia (69, [19.1%]), and dizziness (54, [15%]). Also, 31 patients had neurological complications (8.58%). Anosmia, ageusia, dizziness, and headache were associated with favorable outcome (P < 0.001), while altered mental status and hemiparesis were associated with poor outcome. The mortality rate of patients who had neurological complications was more than twice than that of patients without neurological complication (P = 0.008). Almost half of the patients experienced at least one neurological symptom, which may be the initial presentation of COVID-19. Dementia appears to be associated with severe COVID-19. Mortality was higher in patients with neurological complications, and these patients needed more intensive care.

Medicinal plants remain an invaluable source for therapeutics of diseases that affect humanity. Sideritis bilgeriana (Lamiaceae) is medicinal plant used in Turkey folk medicine to reduce inflammation and pain, but few studies scientific corroborates its medicinal use so creating a gap between popular use and scientific evidence. Thus, we aimed to evaluate the pharmacological effects of the methanolic extract of S. bilgeriana (MESB) in rodents nociception models and also performed its phytochemical analysis. Firstly, a screening was carried out that enabled the identification of the presence of phenolic compounds and flavonoids. In view of this, a chromatographic method by HPLC-DAD-UV was developed that made it possible to identify chlorogenic acid and its quantification in MESB. MESB-treated mice (MESB 50, 100 and 200 mg/kg, p.o.) reduced mechanical hyperalgesia and myeloperoxidase activity (p < 0.01), and also showed a reduced pain behavior in capsaicin test. In the carrageenan-induced pleurisy test, MESB (100 mg/kg p.o.) significantly reduced the leukocyte (polymorphonuclear) count in the pleural cavity and equally decreased the TNF-α and IL-1β levels (p < 0.001). In the PSNL model, mechanical hyperalgesia was reduced on the first evaluation day and during the 7 days of evaluation compared to the vehicle group (p < 0.001). Thermal hyperalgesia was also reduced 1 h after treatment compared to the vehicle group (p < 0.001) and reversed the loss of force initially displayed by the animals, thus inferring an analgesic effect in the muscle strength test. Analysis of the marrow of these animals showed a decrease in the level of pro-inflammatory cytokine IL-6 (p < 0.001) and factor NF-κB, in relation to the control group (p < 0.05). Moreover, the MESB treatment produced no noticeable side effects, no disturb in motor performance and no signs of gastric or hepatic injury. Together, the results suggests that MESB could be useful to management of inflammation and neuropathic pain mainly by the management of pro-inflammatory mediators (NF-κB, TNF-α, IL-1β and IL-6), so reinforcing its use in popular medicine and corroborating the need for further chemical and pharmacological studies for the species., (Copyright © 2020. Published by Elsevier B.V.)

Background: There is inadequate information on the risk of gastrointestinal (GI) bleeding in patients who are under rivaroxaban and warfarin therapy in Iran. Determining the risk of GI bleeding in patients receiving these two drugs can help to select a more appropriate anti-coagulation prophylaxis in high-risk patients., Objective: The aim of this study was to compare the incidence of GI bleeding in patients with atrial fibrillation (AF) and concomitant bleeding risk factors receiving either warfarin or rivaroxaban., Methods: In this observational study, 200 patients with AF and bleeding risk factors who referred to Imam Hossein Hospital (Tehran, Iran) were included. The patients were under treatment with either warfarin or rivaroxaban. The incidence of GI bleeding was compared between the two groups monthly for one year., Results: GI bleedings were observed in 61% and 34% of patients treated with warfarin and rivaroxaban, respectively (P = 0.001).Melena was the most common type of GI bleeding in both groups. History of hypertension, history of stroke, consumption of anti-platelet drugs, NSAID consumption, and history of alcohol consumption were associated with more frequent GI bleeding only in warfarin group., Conclusion: The incidence of GI bleeding was lower in AF patients who received rivaroxaban compared to those treated with warfarin. Also, GI bleeding risk does not change according to the consumption of other anti-coagulant drugs and underlying history of hypertension or stroke in patients received rivaroxaban. Therefore, rivaroxaban is suggested as the choice of prophylaxisin patients with AF and concomitant coagulopathy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

'Candidatus Magnetoglobus multicellularis' is a multicellular magnetotactic prokaryote found in the Araruama lagoon in Rio de Janeiro, Brazil. This microorganism shows a photokinesis that depends on the incident light wavelength, but that dependence can be canceled by the presence of radio-frequency (RF) electromagnetic fields. The present manuscript has as its aim to study the effect of light wavelength and RF fields on the U-turn time of 'Candidatus Magnetoglobus multicellularis', a behavior more related to magnetotaxis. As the experiments were performed during the night, the microorganisms were greater in size than normal, indicating that they were in the process of division. Our results show that when normal in size, the microorganism's U-turn time is modified by the light wavelength (lower for blue light than for green and red light), but RF fields do not affect that U-turn time dependence on the light wavelength. For the microorganism in the process of division, we describe for the first time how the photokinesis and U-turn time dependence on the light wavelength disappear. It is proposed that methyl-accepting chemotaxis proteins are involved in that light wavelength dependence for the U-turn time, but still more studies are necessary to understand how RF fields cancel the photokinesis light wavelength dependence, but do not affect the dependence of the U-turn time.

Purpose: To evaluate the safety and potential healing efficacy of the topical ocular administration of a gelatin membrane containing usnic acid/liposomes (UALs) for corneal cicatrization. UALs have shown healing activity in animal models of dermal burn lesions. We evaluated the safety of topical ocular administration of UAL and its potential healing efficacy as an ophthalmic treatment on chemical lesions in rabbit eyes., Method: The Draize test was used to check for ocular toxicity and the score was zero at each observation, indicating the ocular safety of a gelatin membrane containing usnic acid/liposome. Its potential healing efficacy as an ophthalmic treatment on chemical lesions in rabbit eyes was also assessed., Results: After epithelial removal and treatment with UAL, there was a 49.4 % reduction in injury under in vivo conditions compared with a 36.6 % reduction in the control, a gelatin membrane containing liposome without usnic acid. Histological analysis of ocular surface chemical injury-tissue sections after treatment with UAL supported these observations. The corneal expression of VEGF and TGF-β1increased by 70 % and 50 % respectively following treatment with UAL gelatin membrane., Conclusion: These results indicate the potential therapeutic application of UAL gelatin membranes as an ophthalmic treatment that may be used for corneal cicatrization., (Copyright © 2020 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ethnopharmacological Relevance: Miconia albicans (Melastomataceae), commonly known in Brazil as "canela-de-velho", is used in folk medicine for treating rheumatoid arthritis and reducing pain and inflammation. THE AIM OF THE CURRENT WORK WAS: to provide data on physicochemical characterization of the drug plant and dried extract from M. albicans leaves, as well as investigate the anti-inflammatory effect and antioxidant stress profile from the standardized dried extract of this species employing different model systems., Materials and Methods: plant material (dried crushed leaves) was extracted by turboextraction using 50% ethanol (v/v). Different pharmacological techniques were performed to establish quality control parameters of the plant drug, and dried extract of M. albicans (DEMA) was chemically characterized by HPLC-PDA to selection of the chemical marker. Total phenolic and flavonoid contents were determined by the Folin-Ciocalteu and AlCl 3 colorimetric methods, respectively. Antioxidant potential of the DEMA was investigated by employing different in vitro antioxidant assays, including DPPH and ABTS radical scavenging assays, ferric reducing antioxidant assay, NO scavenging assay, metal ion (Fe 2+ ) chelating activity and antioxidant capacity by inhibition of lipid peroxidation (TBARS). Finally, anti-inflammatory activity of the DEMA was evaluated using two models of acute inflammation: carrageenan induced inflammation and mechanical hyperalgesia., Results and Discussion: M. albicans leaves, after drying in forced air circulation chamber at ±40 °C for 48 h and crushing in knife mill, presented a moisture content below the maximum allowed for plant drugs (6.4%). The powder of M. albicans was classified as moderately coarse and total ash content was found to be 6.27%. Preliminary phytochemical screening of DEMA revealed the presence of flavonoids, tannins, saponins, leucoanthocyanins and steroids. DEMA had significant higher total phenolic (551.3 mg gallic acid equivalent/g of dried extract) and flavonoid contents (367.19 mg catechin equivalent/g of dried extract). Two major compounds (λ = 340 nm) were identified in DEMA by HPLC-PDA: the flavonoids rutin and quercetin. Rutin content, selected as chemical marker, was determined and found to be 1.16 mg/g dried extract (r = 0.9941). Regarding to antioxidant activity, our results revealed the DEMA exhibited good antioxidant activity on different models. M. albicans treatment also reduced the levels of TNF-α e IL-1β and consequently inflammatory nociception and edema caused by carrageenan injection. Based on previous studies and our results, is possible to suggest a positive correlation between the flavonoids rutin and quercetin and the antioxidant and anti-inflammatory capacities., Conclusion: Together, these data suggest that M. albicans has the possibility of use in conditions such as arthritis or other joint pain, even needing other work to better consolidate this profile., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest in this paper., (Copyright © 2020. Published by Elsevier B.V.)

The need to develop new tools and increase capacity to test pharmaceuticals and other chemicals for potential adverse impacts on human health and the environment is an active area of development. Much of this activity was sparked by two reports from the US National Research Council (NRC) of the National Academies of Sciences, Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007) and Science and Decisions: Advancing Risk Assessment (2009), both of which advocated for "science-informed decision-making" in the field of human health risk assessment. The response to these challenges for a "paradigm shift" toward using new approach methodologies (NAMS) for safety assessment has resulted in an explosion of initiatives by numerous organizations, but, for the most part, these have been carried out independently and are not coordinated in any meaningful way. To help remedy this situation, a framework that presents a consistent set of criteria, universal across initiatives, to evaluate a NAM's fit-for-purpose was developed by a multi-stakeholder group of industry, academic, and regulatory experts. The goal of this framework is to support greater consistency across existing and future initiatives by providing a structure to collect relevant information to build confidence that will accelerate, facilitate and encourage development of new NAMs that can ultimately be used within the appropriate regulatory contexts. In addition, this framework provides a systematic approach to evaluate the currently-available NAMs and determine their suitability for potential regulatory application. This 3-step evaluation framework along with the demonstrated application with case studies, will help build confidence in the scientific understanding of these methods and their value for chemical assessment and regulatory decision-making., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Ischaemic stroke represents one of the main causes of disability. According to the broad investigations, it is widely assumed that the contribution of inflammatory mediators is strongly involved in its pathogenesis. Hence, it seems that stroke treatment needs more efficient and inflammatory-targeted compounds to modulate inflammatory-related pathways. Such strategies paved the way to achieve better clinical outcomes along with conventional therapies. Boswellic acids (BAs), the main bioactive compounds of Boswellia sp. resin; are triterpenoids with well-documented anti-inflammatory properties. Compared with NSAIDs, BAs cross blood-brain barrier yet they do not cause serious gastrointestinal adverse effects. Considering BAs anti-inflammatory features, we conducted a randomized double-blind placebo-controlled pilot trial of these compounds as a supplementary therapy. This trial randomized 80 ischaemic stroke patients (40-80-years old) with a 4-20 score according to the National Institutes of Health Stroke Scale (NIHSS), within 72 h of neurological sign onset, in 1-month follow-up period. We assessed NIHSS as primary and plasma levels of TNF-α, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IFN-γ, IP-10, MCP-1, 8-isoprostane, and PGE2 as secondary outcomes. According to NIHSS evaluation, patients who were allocated to BA group had a significant recovery in neurological function during the 1-month follow-up, compared with the placebo. The levels of plasma inflammatory markers were significantly decreased in BA group after 7 days of intervention in TNF-α, IL-1β, IL-6, IL-8, and PGE2. As a preliminary controlled trial in ischaemic stroke, BAs could improve clinical outcome in the early phases of stroke along with promising changes in plasma inflammatory factors.Clinical trial registrationhttps://www.irct.ir Unique identifier: IRCT20170315033086N5. IRCT is a primary registry in the WHO registry network (https://www.who.int/ictrp/network/primary/en/).

Background: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities., Objectives: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats., Methods: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05)., Results: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05)., Conclusions: DL produces bradycardia and antiarrhythmic activity in rat heart.

Citral (CIT) is a monoterpene formed by the geranial and neral stereoisomers. CIT is the major compound of Cymbopogon citratus essential oil, commonly known as "lemongrass", and has demonstrated potential antihyperalgesic, anti-nociceptive and anti-inflammatory effects. However, CIT shows high volatility, low solubility in water and consequent low bioavailability, which limits its use. Therefore, the aim of this study was to evaluate cell viability, anti-hyperalgesic and anti-inflammatory effects of inclusion complexes of CIT on β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). Initially, physical mixture (PM) and freeze-dried inclusion (FD) complexes of CIT/β-CD and CIT/HP-β-CD were obtained in the molar ratio (1:1). The samples were characterized by DSC, TG/DTG, FT-IR, XRD, SEM and the complexation efficiency were performed by HPLC. Cell viability assay was performed by rezasurin reduction technique in J774 macrophages cell line. The motor activity through rota rod apparatus, mechanical hyperalgesia and pleurisy induced by carrageenan were evaluated in mice. The complexation of CIT was evidenced with β-CD and HP-β-CD by the characterization techniques analyzed. The complexation efficiency of CIT/β-CD and CIT/HP-β-CD were 78.6% and 71.7%, respectively. The CIT, CIT/β-CD and CIT/HP-β-CD showed cell viability in macrophages and did not interfere in the motor activity of mice. Besides that, the samples demonstrated antihyperalgesic and anti-inflammatory activity due to the reduction in total leukocytes and TNF-α levels. However, CIT/β-CD has better pharmacological effects among the three samples evaluated. Therefore, CIT/β-CD has potential for the development of products to treat inflammatory and pain reactions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Carvacrol, a phenolic monoterpene derived from thyme oil has gained wide interest recently because of its anticancer activities. To improve the solubility of carvacrol, the formation of inclusion complexes with β-cyclodextrin was performed by ultrasound and freeze-drying methods and characterized using thermal analysis, FTIR, XRD, SEM, NMR and HPLC analysis. From these results, carvacrol was successfully complexed within β-cyclodextrin cavity. Moreover, HPLC analysis demonstrated a higher entrapment efficiency for freeze-drying method (81.20 ± 0.52%) in contrast to ultrasound method (34.02 ± 0.67%). Hence, freeze-drying inclusion complex was evaluated for its antiproliferative effect and cytotoxicity against prostate cancer cell line (PC3) in vitro. Further, freeze-drying complex led to a dose-dependent inhibition in tumor cell growth in 2D and 3D cell culture systems. Altogether, the inclusion of carvacrol in β-cyclodextrin led to the formation of stable complexes with potent antiproliferative effects against PC3 cells, in vitro. Such an improved cytotoxic effect can be attributed to the enhanced the aqueous solubility and bioavailability of carvacrol by effective complexation in β-cyclodextrin., (Copyright © 2019. Published by Elsevier Ltd.)

Background: Migraine is a common disease with neurovascular nature, which is commonly prevalent in the general population. Due to the significant prevalence of migraine and its long-term complications, it is necessary to pay attention to its exacerbating factors. Therefore, the aim of this study was to evaluate the frequency distribution of dyslipidemia in patients with migraine compared with control group., Materials and Methods: This is a case-control study, in which 50 patients with migraine (with aura and without aura) were confirmed by the criteria of International Headache Society. Migraineurs and control group ( n = 50) were selected from among patients who referred to the Neurology Clinic of Imam Hossein Hospital. The levels of total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol were measured in both the groups. SPSS software (version 21) was used to analyze the data., Results: The findings showed that among migraineurs, 21 patients (42%) revealed high levels of cholesterol and 22 revealed high levels of LDL (44%); whereas among subjects without migraine, 12 subjects (24%) exhibited high levels of cholesterol and 12 (24%) high levels of LDL, where a significant correlation between the two groups was achieved., Conclusion: The present results showed that migraine is associated with higher level of cholesterol and LDL when compared with the control group, where a significant relationship was found., Competing Interests: There are no conflicts of interest.

Carpal tunnel syndrome (CTS) is one of the reasons for labor abandonment due to inability and pain. The aim of this study was to evaluate the effectiveness of gabapentin and exercise training in the treatment of CTS and compare their effects. This single-blind clinical trial was conducted on patients referred to the Imam Hossein hospital's electrodiagnostic (EDX) unit. The patients randomly assigned into four groups: using nocturnal splint as an approved treatment in the control group; taking 300-mg gabapentin per night and using nocturnal splint; nerve and tendon gliding exercises and using nocturnal splint; and taking 300-mg gabapentin per night, performing same exercise as group 3 and using nocturnal splint. At baseline, four indicators were assessed in all patients, including the Boston carpal tunnel questionnaire, visual analogue scale (VAS), pinch and grip strength of the affected hand. One month after the beginning of intervention, participants were reassessed and compared for each of the four indicators. Using nocturnal splint along with exercise and gabapentin significantly improved VAS, pinch and grip strength in moderate CTS compared to control group that only used nocturnal splint. However in mild CTS, grip strength was not significantly higher compared to control group ( P =0.048). Results of this study showed that use of splint alone in mild CTS is an appropriate and sufficient treatment; however, in moderate CTS, receiving gabapentin along with exercise and splinting showed better treatment results compared to splinting alone., Competing Interests: CONFLICT OF INTEREST No potential conflict of interest relevant to this article was reported.

Aims: Hypoglycemia can be considered the most common complication of Diabetes Mellitus treatment. So far, controversial studies have been carried out to examine the impacts of hypoglycemia on the cognitive function., Methods: This study was conducted as case-control. The case group was 35 patients with Diabetes Mellitus Types I or II hospitalized in Imam Hussein Hospital, Tehran, Iran, who have experienced hypoglycemic attacks (glucose level below 70 mg/dl). The control group consisted of diabetic patients hospitalized in hospital, but they had no history of hypoglycemia. As the blood glucose level became in normal range and the patients' Mental status became stable, the brain cognitive function was examined using Mini-Mental State test., Results: The mean age of the subjects in the case and control groups was 56.77, 53.73 years old, respectively. The mean cognitive score in the control and hypoglycemic groups was 29.09 and 25.29, respectively. The mean MMSE cognitive score was significantly diminished in the hypoglycemic group (p < 0.001)., Conclusions: This study indicated that incidence of hypoglycemia in diabetic patients is associated with cognitive disorders. Further, there is a linear association between cognitive disorders and hypoglycemia, age and diabetes mellitus complication., (Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

The negative effects triggered by ultraviolet radiation, such as premature aging and carcinogenesis, have motivated several studies on photoprotection. Recent strategies for photoprotection have included the incorporation of natural antioxidant and anti-inflammatory compounds, such as flavonoids, into sunscreens and the oral administration of natural antioxidant extracts. Brazilian Red propolis extract contains isoflavonoids with antioxidant and anti-inflammatory activities. Here, we investigate the photoprotective effects of orally- or topically-administered formulations containing hydroalcoholic extract of red propolis (HERP) in a rodent model. HERP showed markers identified as: daidzein (4.68 μg/mL), formononetin (31.81 μg/mL) and biochanin A (9.58 μg/mL). A fourth peak was found in the chromatogram but was not identified. The antioxidant activity of HERP was calculated to be 3.07 mmol Trolox/g and 2.13 mmol Trolox/g, respectively. Topical HERP exerted a protective action against UVB radiation, which was similar to that exerted by oxybenzone filter. Oral HERP as an adjuvant treatment did not increase sunburn protection. However, the oral administration of HERP presented chemoprotective and anti-inflammatory activity (p < 0.05) similar or better than Polypodium leucotomos oral treatment (positive control). In conclusion, topical administration of HERP has photoprotective activity in a murine model and the mechanisms of protection can be related to the antioxidant and anti-inflammatory characteristics of HERP compounds., (Copyright © 2018. Published by Elsevier B.V.)

Cyclodextrins (CDs) have been widely used as a promising alternative in the formation of inclusion complexes with poorly soluble molecules. From this perspective, the present study aimed to study the inclusion complexes of diosmin in β-cyclodextrin, chemically quantify the diosmin-in-gel preparation and analyze the stability of the gels. Furthermore, we evaluated the effect of therapeutic pulsed ultrasound (TPU) in association with the gel-diosmin complex on the parameters of muscle damage and oxidative stress in rats. Serum creatine kinase (CK) levels were used as an indicator of skeletal muscle injury. Lipid peroxidation (thiobarbituric acid-reactive substances [TBARS]) and superoxide dismutase and catalase activities were used as indicators of oxidative stress. The results obtained indicated that the inclusion complex obtained by co-evaporation had the highest complexation efficiency and stability; there was no change in the features of diosmin on incorporation into the Carbopol gel. Additionally, a significant (p <0.05) decrease was observed in CK levels (TPU plus gel-diosmin: 178.4 ± 85.3 U/L) relative to the untreated group (527.8 ± 46.1 U/L). Levels of TBARS were lower in the TPU plus gel-diosmin group (0.008 ± 0.0004 nmol malondialdehyde/mg protein, p <0.05) compared with the untreated group (0.081 ± 0.011 nmol malondialdehyde/mg protein, p <0.05, n = 6). Catalase activity did not statistically significantly differ between the treatment groups, and superoxide dismutase activity was lower in the diosmin-treated group (0.320 ± 0.11 U/mg protein) compared with the untreated group (0.983 ± 0.40 U/mg protein). These results suggest that TPU in association with the diosmin-gel complex is effective in reducing muscle damage and oxidative stress after mechanical trauma., (Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Hecogenin acetate (HA) is a steroidal sapogenin-acetylated with pharmacological properties which have already been described in the literature such as, anti-inflammatory, anti-hyperalgesic and antinociceptive, but it has low solubility in aqueous media. Therefore, in an attempt to overcome this, we set out to create inclusion complexes between HA and b-cyclodextrin (b-CD) and evaluate the antinociceptive effects in the orofacial nociception in mice. The complexes were prepared using different methods in the molar ratios 1:1 and 1:2 and characterized physicochemically. The results of the physicochemical characterization elucidated inclusion complexes formation between b-CD and HA by freeze drying method in the molar ratio 1:2, which obtained a complexation efficiency of 92% and produced superior analgesic effect in animal models for orofacial pain at a lower dose when compared to HA alone., (Copyright © 2017. Published by Elsevier Masson SAS.)