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Obesity is a major global health epidemic that has adverse effects on both the people affected as well as the cost to society. Several anti-obesity drugs that target GLP-1 receptors have recently come to the market. Here, we describe the effects of tesofensine, a novel anti-obesity drug that acts as a triple monoamine neurotransmitter reuptake inhibitor. Using various techniques, we investigated its effects on weight loss and underlying neuronal mechanisms in mice and rats. These include behavioral tasks, DeepLabCut videotaped analysis, electrophysiological ensemble recordings, optogenetic activation, and chemogenetic silencing of GABAergic neurons in the Lateral Hypothalamus (LH). We found that tesofensine induces a greater weight loss in obese rats than lean rats, while differentially modulating the neuronal ensembles and population activity in LH. In Vgat-ChR2 and Vgat-IRES-cre transgenic mice, we found for the first time that tesofensine inhibited a subset of LH GABAergic neurons, reducing their ability to promote feeding behavior, and chemogenetically silencing them enhanced tesofensine's food-suppressing effects. Unlike phentermine, a dopaminergic appetite suppressant, tesofensine causes few, if any, head-weaving stereotypy at therapeutic doses. Most importantly, we found that tesofensine prolonged the weight loss induced by 5-HTP, a serotonin precursor, and blocked the body weight rebound that often occurs after weight loss. Behavioral studies on rats with the tastant sucrose indicated that tesofensine's appetite suppressant effects are independent of taste aversion and do not directly affect the perception of sweetness or palatability of sucrose. In summary, our data provide new insights into the effects of tesofensine on weight loss and the underlying neuronal mechanisms, suggesting that tesofensine may be an effective treatment for obesity and that it may be a valuable adjunct to other appetite suppressants to prevent body weight rebound., Competing Interests: RG is soliciting a patent for the homegustometer behavioral equipment., (Copyright: © 2024 Perez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Acute aortic syndromes (AAS) include a variety of overlapping anatomical and clinical conditions. Intramural hematoma (IMH), penetrating aortic ulcer, and aortic dissection occur in isolation or may coexist in the same patient. IMH represents 5-30% of all AAS and 60-70% of cases are located in the descending aorta. The diagnosis relies on a high index of clinical suspicion and on the use of complementary images. Management is conservative, but patients with some high-risk characteristics have a higher risk of mortality in the acute phase, so initial endovascular management should be considered. We present the case of a 69-year-old patient, in whom IMH was diagnosed in the course of a hypertensive emergency and who required hybrid management due to high-risk anatomical characteristics for endovascular management only., Competing Interests: Conflictos de interés: Los autores declaran no tener ningún conflicto de interés

Cigarette butts (CB) and cigarette butt fibers (CBF) are highly abundant and frequent residues on beach sand. Also, they are hazardous waste due to their significant toxicity and potential risk to the ecosystems' biota and the health of beach tourists. This study aimed to determine the abundance and density of CB and CBF found on the active, rest, and service zones of five pilot beaches in Argentina, Colombia, Brazil, Ecuador, and Mexico. The methodology involved collecting CB and CBF in 500 m 2 transects of urban tourist beaches using a citizen science-adapted methodology between June 2021 and May 2022, during the COVID-19 pandemic. The abundance and density of CB and CBF, and the Cigarette Butt Pollution Index (CBPI) were calculated. The highest proportion of CB was found in service and rest areas. Bocagrande (CO) reported the highest generation of CB and CBF and a severe CBPI., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

In this work, the SET and RESET processes of bipolar resistive switching memories with silicon nanocrystals (Si-NCs) embedded in an oxide matrix is simulated by a stochastic model. This model is based on the estimation of two-dimensional oxygen vacancy configurations and their relationship with the resistive state. The simulation data are compared with the experimental current-voltage data of Si-NCs/SiO2 multilayer-based memristor devices. Devices with 1 and 3 Si-NCs/SiO2 bilayers were analyzed. The Si-NCs are assumed as agglomerates of fixed oxygen vacancies, which promote the formation of conductive filaments (CFs) through the multilayer according to the simulations. In fact, an intermediate resistive state was observed in the forming process (experimental and simulated) of the 3-BL device, which is explained by the preferential generation of oxygen vacancies in the sites that form the complete CFs, through Si-NCs.

Osteoporosis management has become more relevant as the life expectancy increases. In Ecuador, approximately 19% of adults over 65 years of age have been diagnosed with osteoporosis. There is no national consensus for the management and prevention of the disease being this proposal the first Ecuadorian consensus., Introduction: In Ecuador, it is estimated that around 19% of adults over 65 years of age have osteoporosis. Due to the increase in life expectancy in the world population, the evaluation and management of osteoporosis has become more relevant. Currently, there is no national consensus for the management and prevention of the disease. The Ecuadorian Society of Rheumatology presented the project for the elaboration of the first Ecuadorian consensus for the management and prevention of osteoporosis., Methods: A panel of experts in multiple areas and extensive experience was invited to participate. The consensus was carried out using the Delphi method. Six working dimensions were created: definition and epidemiology of osteoporosis, fracture risk prediction tools, non-pharmacological treatment, pharmacological treatment, calcium and vitamin D, and glucocorticoid-induced osteoporosis., Results: The first round was held in December 2021, followed by the second round in February 2022 and the third round in March 2022. The data was shared with the specialists at the end of each round. After three rounds of work, a consensus was reached for the management and prevention of osteoporosis., Conclusion: This is the first Ecuadorian consensus for the management and treatment of postmenopausal osteoporosis., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

In this work, we report the digital and analog resistive-switching (RS) characteristics in a memristor based on silicon nanocrystals (Si-NCs) integrated into a complementary metal-oxide-semiconductor (MOS) structure. Si-NCs with a diameter of 5.48 ± 1.24 nm embedded in a SiO 2 /Si-NCs/SiO 2 multilayer structure acts as an RS layer. These devices exhibit bipolar RS with an intermediate resistance step during SET and RESET processes, which is believed to lie in the Si-NCs layer acting as charge-trapping nodes. The endurance studies of about 70 DC cycles indicate an ON/OFF ratio of ~10 6 and a retention time larger than 10 4 s. Long-term potentiation (LTP, -2 V) and long-term depression (LTD, +4 V) are obtained by applying consecutive identical pulse voltages of 150 ms duration. The current value gradually increases/decreases (LTP/LTD) as the pulse number increases. Three consecutive identical pulses of -2 V/150 ms (LTP) separated by 5 and 15 min show that the last current value obtained at the end of each pulse train is kept, confirming an analog RS behavior. These characteristics provide a possible way to mimic biological synapse functions for applications in neuromorphic computing in Si-NCs-based CMOS structures.

In this work, we explored the feasibility of the fabrication of PIN light-emitting diodes (LEDs) consisting of heterojunctions of amorphous silicon-carbide (a-Si 1-x C x :H) thin films and crystalline silicon wafers (c-Si). The objective is the future development of electro-photonic systems in the same c-Si wafer, containing transistors, sensors, LEDs and waveguides. Two different heterojunction LEDs were fabricated consisting of PIN and PIN + N structures, where a-Si 1 -x C x :H thin films were used as P-type and I-type layers, while an N-type c-Si substrate was used as an active part of the device. The amorphous layers were deposited by the plasma-enhanced chemical vapor deposition (PECVD) technique at a substrate temperature of 200 °C. The PIN device presented electroluminescence (EL) only in the forward bias, while the PIN + N device presented in both the forward and reverse biases. The EL in reverse bias was possible due to the addition of an N + -type a-Si:H layer between the c-Si substrate and the I-type a-Si 1 -x C x :H active layer. Likewise, the EL intensity of the PIN + N structure was higher than that of the PIN device in forward bias, indicating that the addition of the N-type a-Si:H layer makes electrons flow more efficiently to the I layer. In addition, both devices presented red EL in the full area, which is observed with the naked eye.

In this work, we show a correlation between the composition and the microstructural and optical properties of bright and uniform luminescent porous silicon (PSi) films. PSi films were synthesized by electrochemical etching using nitric acid in an electrolyte solution. PSi samples synthesized with nitric acid emit stronger (up to six-fold greater) photoluminescence (PL) as compared to those obtained without it. The PL peak is shifted from 630 to 570 nm by changing the concentration ratio of the HF:HNO 3 :(EtOH-H 2 O) electrolyte solution, but also shifts with the excitation energy, indicating quantum confinement effects in the silicon nanocrystals (Si-NCs). X-ray photoelectron spectroscopy analysis shows a uniform silicon content in the PSi samples that emit the strongest PL. High-resolution transmission electron microscopy reveals that the Si-NCs in these PSi samples are about ~2.9 ± 0.76 nm in size and are embedded in a dense and stoichiometric SiO 2 matrix, as indicated by the Fourier transform infrared analysis. On the other hand, the PSi films that show PL of low intensity present an abrupt change in the silicon content depth and the formation of non-bridging oxygen hole center defects.

A novel method to extract the seven parameters of the double-diode model of solar cells using the current-voltage (I-V) characteristics under illumination and in the dark is presented. The algorithm consists of two subroutines which are alternatively run to adjust all the parameters of the cell in an iterative process. Curve fitting of the light I-V characteristics ensures accuracy in the prediction of the maximum power point, whereas simultaneously fitting the dark I-V characteristics results in a set of physically meaningful parameters that provide information about the physical performance of the photovoltaic devices. Experimental I-V curves of in-house solar cells are used to validate the proposed parameter extraction method, which can be furthermore applied to other types of p-n junction-based photovoltaic devices.

Hydrogenated microcrystalline silicon (µc-Si:H) and epitaxial silicon (epi-Si) films have been produced from SiF 4 , H 2 and Ar mixtures by plasma enhanced chemical vapor deposition (PECVD) at 200 °C. Here, both films were produced using identical deposition conditions, to determine if the conditions for producing µc-Si with the largest crystalline fraction (X C ), will also result in epi-Si films that encompass the best quality and largest crystalline silicon (c-Si) fraction. Both characteristics are of importance for the development of thin film transistors (TFTs), thin film solar cells and novel 3D devices since epi-Si films can be grown or etched in a selective manner. Therefore, we have distinguished that the H 2 /SiF 4 ratio affects the X C of µc-Si, the c-Si fraction in epi-Si films, and the structure of the epi-Si/c-Si interface. Raman and UV-Vis ellipsometry were used to evaluate the crystalline volume fraction (Xc) and composition of the deposited layers, while the structure of the films were inspected by high resolution transmission electron microscopy (HRTEM). Notably, the conditions for producing µc-Si with the largest X C are different in comparison to the fabrication conditions of epi-Si films with the best quality and largest c-Si fraction.

Two multilayer (ML) structures, composed of five layers of silicon-rich oxide (SRO) with different Si contents and a sixth layer of silicon-rich nitride (SRN), were deposited by low pressure chemical vapor deposition. These SRN/SRO MLs were thermally annealed at 1100 °C for 180 min in ambient N 2 to induce the formation of Si nanostructures. For the first ML structure (MLA), the excess Si in each SRO layer was about 10.7 ± 0.6, 9.1 ± 0.4, 8.0 ± 0.2, 9.1 ± 0.3 and 9.7 ± 0.4 at.%, respectively. For the second ML structure (MLB), the excess Si was about 8.3 ± 0.2, 10.8 ± 0.4, 13.6 ± 1.2, 9.8 ± 0.4 and 8.7 ± 0.1 at.%, respectively. Si nanopyramids (Si-NPs) were formed in the SRO/Si substrate interface when the SRO layer with the highest excess silicon (10.7 at.%) was deposited next to the MLA substrate. The height, base and density of the Si-NPs was about 2-8 nm, 8-26 nm and ~6 × 10 11 cm -2 , respectively. In addition, Si nanocrystals (Si-ncs) with a mean size of between 3.95 ± 0.20 nm and 2.86 ± 0.81 nm were observed for the subsequent SRO layers. Meanwhile, Si-NPs were not observed when the excess Si in the SRO film next to the Si-substrate decreased to 8.3 ± 0.2 at.% (MLB), indicating that there existed a specific amount of excess Si for their formation. Si-ncs with mean size of 2.87 ± 0.73 nm and 3.72 ± 1.03 nm were observed for MLB, depending on the amount of excess Si in the SRO film. An enhanced photoluminescence (PL) emission (eight-fold more) was observed in MLA as compared to MLB due to the presence of the Si-NPs. Therefore, the influence of graded silicon content in SRN/SRO multilayer structures on the formation of Si-NPs and Si-ncs, and their relation to the PL emission, was analyzed.

Early childhood is a critical period for obesity prevention. This randomized controlled study evaluated the effectiveness of an educational intervention preventing obesity in preschool-age children. A nutritional education intervention, with a follow-up session one year later, was conducted with parents of children aged 3 to 4 years of public schools in the province of Málaga. The main outcome variable was the body mass index z-score (zBMI). The prevalence of overweight or obesity was the secondary outcome variable. The sample comprised 261 students (control group = 139). Initial BMI, weight, height-for-age and prevalence of overweight and obesity were similar for both groups. After the first year of the intervention, the zBMI of the intervention group decreased significantly from 0.23 to 0.10 ( p = 0.002), and the subgroup of patients with baseline zBMI above the median decreased from 1 to 0.72 ( p = 0.001), and in the second year from 1.01 to 0.73 ( p = 0.002). The joint prevalence of overweight and obesity increased in the control group (12.2% to 20.1%; p = 0.027), while in the intervention group, there were no significant changes. This preschool educational intervention with parents improved their children's BMI, especially those with a higher BMI for their age, and favored the prevention of overweight or obesity.

The applicability of the path planning strategy to robotic manipulators has been an exciting topic for researchers in the last few decades due to the large demand in the industrial sector and its enormous potential development for space, surgical, and pharmaceutical applications. The automation of high-degree-of-freedom (DOF) manipulator robots is a challenging task due to the high redundancy in the end-effector position. Additionally, in the presence of obstacles in the workspace, the task becomes even more complicated. Therefore, for decades, the most common method of integrating a manipulator in an industrial automated process has been the demonstration technique through human operator intervention. Although it is a simple strategy, some drawbacks must be considered: first, the path's success, length, and execution time depend on operator experience; second, for a structured environment with few objects, the planning task is easy. However, for most typical industrial applications, the environments contain many obstacles, which poses challenges for planning a collision-free trajectory. In this paper, a multiple-query method capable of obtaining collision-free paths for high DOF manipulators with multiple surrounding obstacles is presented. The proposed method is inspired by the resistive grid-based planner method (RGBPM). Furthermore, several improvements are implemented to solve complex planning problems that cannot be handled by the original formulation. The most important features of the proposed planner are as follows: (1) the easy implementation of robotic manipulators with multiple degrees of freedom, (2) the ability to handle dozens of obstacles in the environment, (3) compatibility with various obstacle representations using mathematical models, (4) a new recycling of a previous simulation strategy to convert the RGBPM into a multiple-query planner, and (5) the capacity to handle large sparse matrices representing the configuration space. A numerical simulation was carried out to validate the proposed planning method's effectiveness for manipulators with three, five, and six DOFs on environments with dozens of surrounding obstacles. The case study results show the applicability of the proposed novel strategy in quickly computing new collision-free paths using the first execution data. Each new query requires less than 0.2 s for a 3 DOF manipulator in a configuration space free-modeled by a 7291 × 7291 sparse matrix and less than 30 s for five and six DOF manipulators in a configuration space free-modeled by 313,958 × 313,958 and 204,087 × 204,087 sparse matrices, respectively. Finally, a simulation was conducted to validate the proposed multiple-query RGBPM planner's efficacy in finding feasible paths without collision using a six-DOF manipulator (KUKA LBR iiwa 14R820) in a complex environment with dozens of surrounding obstacles.

Background: Rheumatic diseases are a reason for frequent consultation with primary care doctors. Unfortunately, there is a high percentage of misdiagnosis., Objective: To design an algorithm to be used by primary care physicians to improve the diagnostic approach of the patient with joint pain, and thus improve the diagnostic capacity in four rheumatic diseases., Methods: Based on the information obtained from a literature review, we identified the main symptoms, signs, and paraclinical tests related to the diagnosis of rheumatoid arthritis, spondyloarthritis with peripheral involvement, systemic lupus erythematosus with joint involvement, and osteoarthritis. We conducted 3 consultations with a group of expert rheumatologists, using the Delphi technique, to design a diagnostic algorithm that has as a starting point "joint pain" as a common symptom for the four diseases., Results: Thirty-nine rheumatologists from 18 countries of Ibero-America participated in the Delphi exercise. In the first consultation, we presented 94 items to the experts (35 symptoms, 31 signs, and 28 paraclinical tests) candidates to be part of the algorithm; 74 items (25 symptoms, 27 signs, and 22 paraclinical tests) were chosen. In the second consultation, the decision nodes of the algorithm were chosen, and in the third, its final structure was defined. The Delphi exercise lasted 8 months; 100% of the experts participated in the three consultations., Conclusion: We present an algorithm designed through an international consensus of experts, in which Delphi methodology was used, to support primary care physicians in the clinical approach to patients with joint pain. Key Points • We developed an algorithm with the participation of rheumatologists from 18 countries of Ibero-America, which gives a global vision of the clinical context of the patient with joint pain. • We integrated four rheumatic diseases into one tool with one common symptom: joint pain. It is a novel tool, as it is the first algorithm that will support the primary care physician in the consideration of four different rheumatic diseases. • It will improve the correct diagnosis and reduce the number of paraclinical tests requested by primary care physicians, in the management of patients with joint pain. This point was verified in a recently published study in the journal Rheumatology International (reference number 31).

Background: Vitamin D (VD) deficiency is a global pandemic that affects more than a third of the population worldwide. The population of Latin America and the Caribbean exceeds 620 million inhabitants with diverse ethnic origins and different latitudes and altitudes, which make comparisons and generalizations difficult., Aim and Method: We sought to establish an expert consensus regarding the recommendations for VD supplementation in Latin America by means of the Delphi methodology., Results: The prophylactic dosage of VD in the general population should be individualized according to age, race, body weight, sun exposure of an individual, altitude, and dietary and exercise habits, without ruling out existing chronic diseases., Conclusion: The importance of VD has been widely documented and its deficiency is a pandemic. Many individuals have difficulty meeting daily VD requirements through food and the sun. The population of Latin America and the Caribbean has diverse ethnics, cultures, in addition to living in different latitudes and altitudes. Therefore, it is important to make a position on VD supplementation, given the different characteristics, ages and serum levels of 25(OH)D.

D-norpseudoephedrine (NPE), also known as cathine, is found naturally in the shrub Catha edulis "Khat." NPE has been widely used as an appetite suppressant for the treatment of obesity. Although it is known that NPE acts on α1-adrenergic receptors, there is little information about the role of dopamine receptors on NPE's induced anorectic and weight loss effects. Equally untouched is the question of how NPE modulates neuronal activity in the nucleus accumbens shell (NAcSh), a brain reward center, and a pharmacological target for many appetite suppressants. To do this, in rats, we characterized the pharmacological effects induced by NPE on weight loss, food intake, and locomotion. We also determined the involvement of dopamine D1- and D2-like receptors using systemic and intra-NAcSh antagonists, and finally, we recorded single-unit activity in the NAcSh in freely moving rats. We found that NPE decreased 24-h food intake, induced weight loss, and as side effects increased locomotor activity and wakefulness. Also, intraperitoneal and intra-NAcSh administration of D1 and D2 dopamine antagonists partially reversed NPE's induced weight loss and food intake suppression. Furthermore, the D1 antagonist, SCH-23390, eliminated NPE-induced locomotion, whereas the D2 antagonist, raclopride, only delayed its onset. We also found that NPE evoked a net activation imbalance in NAcSh that propelled the population activity trajectories into a dynamic pharmacological brain state, which correlated with the onset of NPE-induced wakefulness. Together, our data demonstrate that NPE modulates NAcSh spiking activity and that both dopamine D1 and D2 receptors are necessary for NPE's induced food intake suppression and weight loss., (Copyright © 2020 Kalyanasundar, Perez, Arroyo, Moreno and Gutierrez.)

Objective: To evaluate the impact of an intervention package on maternal and newborn health indicators., Methods: A randomized stepped-wedge non-blind trial was conducted across six subdistricts within two districts in Guatemala from January 2014 to January 2017. Data on outcomes were collected on all deliveries in all 33 health centers. The intervention package included distribution of promotional materials encouraging health center delivery; education for traditional birth attendants about the importance of health center delivery; and provider capacity building using simulation training. Main outcomes were number of health center deliveries, maternal morbidity, and perinatal morbidity and mortality., Results: Overall, there were 24 412 deliveries. Health center deliveries per 1000 live births showed an overall increase, although after adjustment for secular trends and clustering, the relative risk for the treatment effect was not statistically significant (aRR, 1.04; 95% confidence interval [CI], 0.97-1.11, P=0.242). Although not statistically significant, maternal morbidity (aRR, 0.78; 95% CI, 0.60-1.02; P=0.068) and perinatal morbidity (aRR, 0.84; 95% CI, 0.68-1.05; P=0.133) showed a tendency toward a decrease., Conclusion: The present study represents one of the few randomized evaluations of an integrated approach to improve birth outcomes in a low-income setting. ClinicalTrials.gov: NCT0315107., (© 2020 International Federation of Gynecology and Obstetrics.)

Introduction: Disability in RA is associated with loss of workdays, greater use of health resources and a higher prevalence of depression. The purpose of this study was to determine the prevalence of functional disability and the factors associated with it., Methods: A cross-sectional study was carried out during January-June 2019 at a rheumatology clinic in the city of Guayaquil. Patients with pre-established RA were included. Functional disability was measured using the HAQ-DI. Data were analyzed using the statistical program SPSS v22. We compared characteristics between patients with and without disability using Student's t -test and chi-square. A multiple logistic regression model for functional disability was made., Results: We included 395 patients, 87.8% female and 12.2% male with a mean age of 51.4±12 years and mean duration of disease 13.8±7 years. Most patients had extra-articular manifestations (80.8%) and comorbidities (81.3%). The mean HAQ-DI was 0.8±0.9, with a prevalence of disability of 26.6%. We found a statistically significant relationship between disability and female sex (p=0.018), age (p=0.020), presence of extra-articular manifestations (p=0.008), myalgia (p<0.001) and fatigue (p<0.001). In addition, patients with disabilities had a lower employment rate (26.7%) compared to those without disability (45.5%, p=0.001). In the multivariate logistic analysis, only depression (p=0.029), diabetes (p=0.003), SJC (p=0.001) and VAS of pain (p=0.004) were significantly related to functional disability., Conclusion: Disability affects a quarter of patients with RA. Among the determinants of disability, we found female sex, older age, grade of pain, inflammatory markers and the level of disease activity., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Intriago et al.)

In this paper, the photoluminescence (PL) of hydrogenated amorphous silicon carbide (a-Si 1-x C x :H) thin films obtained by Plasma Enhancement Chemical Vapor Deposition (PECVD) is reported. Strong PL is obtained after a fast annealing process for 60 s at temperatures of 200, 400, 600, and 800 °C. The thin films are characterized using Fourier Transform Infrared spectroscopy (FTIR), PL spectroscopy, and Energy-Dispersive X-ray Spectroscopy (EDS). According to the results of the structural characterization, it is deduced that a structural rearrangement of the amorphous matrix is carried out during the fast annealing process, which results in different degrees of oxidation on the a-Si 1-x C x :H films. The PL peak position shifts towards higher energies as the temperature increases. The sample deposited with a silane/methane flux ratio of 37.5 at an Radio Frequency (RF) power of 6 W experiences an increase in PL intensity of more than nine times, with a displacement in the peak position from 2.5 eV to 2.87 eV, at 800 °C. From the PL analysis, we observe two emission bands: one centered in the near infrared and other in the visible range (with a blue peak). This study opens the possibility to use such thin films in the development of optoelectronics devices, with potential for application in solar cells.

This work reports the development of arrays of infrared sensors (microbolometers) using a hydrogenated polymorphous silicon-germanium alloy (pm-Si x Ge 1-x :H). Basically, polymorphous semiconductors consist of an amorphous semiconductor matrix with embedded nanocrystals of about 2-3 nm. The pm-Si x Ge 1-x :H alloy studied has a high temperature coefficient of resistance (TCR) of 4.08%/K and conductivity of 1.5 × 10 -5 S∙cm -1 . Deposition of thermosensing film was made by plasma-enhanced chemical vapor deposition (PECVD) at 200 °C, while the area of the devices is 50 × 50 μm 2 with a fill factor of 81%. Finally, an array of 19 × 20 microbolometers was packaged for electrical characterization. Voltage responsivity values were obtained in the range of 4 × 10 4 V/W and detectivity around 2 × 10 7 cm∙Hz 1/2 /W with a polarization current of 70 μA at a chopper frequency of 30 Hz. A minimum value of 2 × 10 -10 W/Hz 1/2 noise equivalent power was obtained at room temperature. In addition, it was found that all the tested devices responded to incident infrared radiation, proving that the structure and mechanical stability are excellent.

Under paradigms of combined intravenous cocaine and ethanol self-administration, the effects on behavior have been poorly explored. Numerous studies have found sex differences in amino acids profile and behavioral responses to each drug, yet few have focused on the interactions between cocaine and ethanol. The main objective of this work was to explore the acquisition and maintenance of intravenous self-administration behavior with a combination of cocaine and ethanol in male and female young adult rats. Likewise, the amino acids profile in blood plasma was quantified 48 hours after the last self-administration session. Male and female 52 days old Wistar rats were randomly assigned to one of 3 groups: i) saline control, ii) cocaine (1 mg/kg bodyweight/injection) and iii) cocaine and ethanol (1 mg + 133 mg/kg bodyweight/ injection). After 24 self-administration sessions carried out on a fixed-ratio-1 schedule, with a limit of 15 doses per session, 14 plasma amino acids were quantified by mean Capillary Electrophoresis technique. The curve of cocaine and ethanol combined self-administration was similar to that associated with cocaine administration alone, with females acquiring self-administration criterion before males. The self-administration of cocaine and ethanol altered the plasma concentration and relative ratios of the amino acid L-Tyrosine. In our intravenous self-administration model, females appeared more vulnerable to acquire abusive consumption of the cocaine and ethanol combination, which altered plasma L-Tyrosine levels., Competing Interests: The authors have declared that no competing interests exist.

Dual-energy X-ray absorptiometry is recognized for measuring bone mineral density. The lack of knowledge can lead to errors both in the acquisition of information and in its analysis and subsequent interpretation. The main errors in Ecuadorian Centers were positioning of the patient to the equipment and incorrect analyzed area., Purpose/introduction: Dual-energy X-ray absorptiometry (DXA) is recognized as the gold standard for measuring bone mineral density (BMD) with acceptable errors, good precision, and reproducibility. However, the training of operators in different centers and countries is not standardized, and the lack of knowledge can lead to errors both in the acquisition of information and in its analysis and subsequent interpretation. The purpose was to determine the most common errors in the performance of bone densitometry from different imaging centers in Ecuador., Methods: Cross-sectional descriptive study. We collected DXA scans from different imaging centers in Ecuador. Data from the DXA scan included city of origin, type of specialist that requested it, and densitometry diagnosis. The DXA images provided were analyzed double blind by experts in the field from Argentina., Results: From a total of 141 patients with a mean age of 61 ± 10 years, 93.6% were women. About 78% of the DXA scans came from private imaging centers and 22% from public centers, 95% of all came from the city of Guayaquil. The machines used were Hologic 50.4% and Lunar 49.6%. The densitometric diagnosis was 16.3% normal, 46.1% osteoporosis, and 37.6% osteopenia. A total of 112 left hip and 49 right hip scans were analyzed from which 31.2% and 22.4% had errors in patient positioning, respectively, mainly internal or external rotation. About 140 lumbar scans were analyzed from which 21.4% had patient positioning errors (not centered or not straight). Also in 38.5% the vertebral area did not correspond to L1-L4. About 3.5% had artifacts such as a metal bar or implant. The region of interest was misplaced in 24.1% of the lumbar scans and 19.9% of the femur., Conclusions: DXA quality standards exist but are often not implemented in clinical practice. When studies are performed incorrectly, it can lead to important errors in diagnosis and therapy. Physicians interested in the management of osteoporosis, although not directly involved in the performance and interpretation of DXA, should be familiar with the protocols to minimize errors and allow the proper use of bone densitometry.

Obesity has become a serious public health problem. Although diet, surgery, and exercise are the primary treatments for obesity, these activities are often supplemented using appetite suppressants. A previous study reported that obesity specialists frequently prescribed a new drug combination for its treatment that includes phentermine (Phen; dopaminergic appetite suppressant), a serotonin (5-HT) precursor 5-hydroxytryptophan (5-HTP; an appetite suppressant that increases the 5-HT concentration), and carbidopa (CB; peripheral blocker of conversion of 5-HTP to 5-HT). Despite its widespread use, there is neither a preclinical study confirming the drug efficacy nor studies of its effects on the brain. To fill this gap, in rats for seven consecutive days, we administered Phen intraperitoneally at different doses either alone or in combination with a fixed dose of 5-HTP/CB. In a different group, we infused drugs via an intraperitoneal catheter while extracellular-recordings were performed in the nucleus accumbens shell (NAcSh), a brain region with dopamine-releasing effects that is involved in the action of appetite suppressants. We found that the triple-drug combination leads to greater weight-loss than each drug alone. Moreover, and as the treatment progresses, the triple drug combination partially reversed psychomotor side-effects induced by Phen. Electrophysiological results revealed that Phen alone evoked a net inhibitory imbalance in NAcSh population activity that correlated with the onset of psychomotor effects. In addition, and unlike the greater weight loss, the addition of 5-HTP/CB did not alter the Phen-evoked inhibitory imbalance in NAcSh responses. Subsequent experiments shed light on the underlying mechanism. That is the majority of NAcSh neurons modulated by 5-HTP/CB were suppressed by Phen. Notably, and despite acting via a different mechanism of action (DA for Phen vs. 5-HT for 5-HTP/CB), both drugs recruited largely overlapping NAcSh neuronal ensembles. These data suggest that the neural correlates of the greater weight loss could be located outside the NAcSh, in other brain circuits. Furthermore, we conclude that Phen + 5-HTP/CB is a potential treatment for overweight and obesity., (Copyright © 2019 Perez, Kalyanasundar, Moreno and Gutierrez.)

Bezoar is an accumulation of organic substances in the gastrointestinal tract; trichobezoar refers to the accumulation of hair usually in the stomach and even beyond it (Rapunzel syndrome). The incidence of this condition is extremely rare, 90 % of cases occur in women, and 80 % of these occur in those under 30 years of age and are related to anxiety behaviors and psychiatric disorders. The integral approach in these patients is fundamental, together with the interdisciplinary follow-up, treating the underlying psycho-emotional causes and adequate psychoeducation with the patients and their relatives, in order to reduce the risk of possible recurrences. We present the clinical case of a patient of school age, with a history of physical abuse by her stepfather and subsequent anxious behaviors (trichotillomania and trichophagia)., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Zeolite/nanoparticle composites are synthesized and used as additive for waterborne formulations in replacement of traditional isothiazolinone-based biocides. Silver nanoparticles dispersed onto micrometer-sized crystals of A-type zeolite were prepared by thermal treatment or chemical reduction methods applied to the Ag-exchanged zeolite. The antifungal efficiency against Trichoderma sp. of waterborne outdoor coatings containing the supported silver nanoparticles, measured in terms of inhibition halo development, shows similar results to those obtained by using traditional organic biocides, the type, size and size distribution of the nanoparticles being the main factors affecting the biocidal action of the prepared coatings., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Extracellular recordings of electrical activity in freely moving rats are fundamental to understand brain function in health and disease. Such recordings require a small-size, lightweight device that includes movable electrodes (microdrive) to record either a new set of neurons every day or the same set of neurons over time. Ideally, microdrives should be easy to implant, allowing precise and smooth displacement of electrodes. The main caveat of most commercially available microdrives is their relatively short half-life span, in average ranging from weeks to a month. For most experiments, recording days-weeks is sufficient, but when the experiment depends on training animals for several months, it is crucial to develop new approaches. Here, we present a low-cost, reusable, and reimplantable device design as a solution to extend chronic recordings to long-term. This device is composed of a baseplate that is permanently fixed to the rodent's skull, as well as a reusable and replaceable microdrive that can be attached and detached from the baseplate, allowing its implantation and reimplantation. Reimplanting this microdrive is particularly convenient when no clear neuronal signal is present, or when the signal gradually decays across days. Our microdrive incorporates a mechanism for moving a 16 tungsten-wire bundle within a small (∼15 mm 3 ) lightweight device (∼4 g). We present details of the design, manufacturing, and assembly processes. As a proof of concept, we show that recordings of the nucleus accumbens core (NAcc) in a freely behaving rat are stable over a month. Additionally, during a lever-press task, we found, as expected, that NAc single-unit activity was associated with rewarded lever presses. Furthermore, we also show that NAc shell (NAcSh) responses evoked by freely licking for sucrose, consistent with our previously published results, were conserved from a first implant to a second microdrive reimplant in the same rat, notably showing reimplantation is possible without overtly affecting the functional responses of the area of interest. In sum, here we present a novel microdrive design (low-cost, small size, and light weight) that can be used for long-term chronic recordings and reimplanted in freely behaving rats.

This study reports the optical, structural, electrical and dielectric properties of Poly (vinyl alcohol) thin films membranes with embedded ZnO nanoparticles (PVA/ZnO) obtained by the solution casting method at low temperature of deposition. Fourier Transform Infrared spectra showed the characteristics peaks, which correspond to O⁻H and Zn⁻O bonds present in the hybrid material. The X-ray diffraction patterns indicated the presence of ZnO structure into the films. The composite material showed low absorbance and a wide band of gap energy from 5.5 to 5.83 eV. The surface morphology for the thin films of PVA/ZnO was studied by Atomic Force Microscopy and Scanning Electron Microscopy. The electrical properties of the membranes were also characterized by current-voltage characteristics and the DC conductivity showed Arrhenius behavior with values of activation energy from 0.62 to 0.78 eV and maximum conductivity at 2.4 × 10 -12 S/cm. The dielectric properties of the nanocomposites were measured from low to high frequencies, and the results showed a high dielectric constant ( ε ) in the order of 10⁴ at low frequency and values from ε ≈ 2000 to 100 in the range of 1 KHz⁻1 MHz respectively. The properties of PVA/ZnO such as the high permittivity and the low temperature of processing make it a suitable material for potential applications in the development of flexible electronic devices.

Although the palatability of sucrose is the primary reason for why it is over consumed, it is not well understood how it is encoded in the nucleus accumbens shell (NAcSh), a brain region involved in reward, feeding, and sensory/motor transformations. Similarly, untouched are issues regarding how an external auditory stimulus affects sucrose palatability and, in the NAcSh, the neuronal correlates of this behavior. To address these questions in behaving rats, we investigated how food-related auditory cues modulate sucrose's palatability. The goals are to determine whether NAcSh neuronal responses would track sucrose's palatability (as measured by the increase in hedonically positive oromotor responses lick rate), sucrose concentration, and how it processes auditory information. Using brief-access tests, we found that sucrose's palatability was enhanced by exteroceptive auditory cues that signal the start and the end of a reward epoch. With only the start cue the rejection of water was accelerated, and the sucrose/water ratio was enhanced, indicating greater palatability. However, the start cue also fragmented licking patterns and decreased caloric intake. In the presence of both start and stop cues, the animals fed continuously and increased their caloric intake. Analysis of the licking microstructure confirmed that auditory cues (either signaling the start alone or start/stop) enhanced sucrose's oromotor-palatability responses. Recordings of extracellular single-unit activity identified several distinct populations of NAcSh responses that tracked either the sucrose palatability responses or the sucrose concentrations by increasing or decreasing their activity. Another neural population fired synchronously with licking and exhibited an enhancement in their coherence with increasing sucrose concentrations. The population of NAcSh's Palatability-related and Lick-Inactive neurons were the most important for decoding sucrose's palatability. Only the Lick-Inactive neurons were phasically activated by both auditory cues and may play a sentinel role monitoring relevant auditory cues to increase caloric intake and sucrose's palatability. In summary, we found that auditory cues that signal the availability of sucrose modulate its palatability and caloric intake in a task dependent-manner and had neural correlates in the NAcSh. These findings show that exteroceptive cues associated with feeding may enhance positive hedonic oromotor-responses elicited by sucrose's palatability.

The structural effect of neurturin (NRTN) on the nigrostriatal dopaminergic system in animals remains unknown, although NRTN has been shown to be effective in Parkinson's disease animal models. Herein, we aimed to demonstrate that NRTN overexpression in dopaminergic neurons stimulates both neurite outgrowths in the nigrostriatal pathway and striatal dendritic spines in aging rats with chronic 6-hydroxydopamine (6-OHDA) lesion. At week 12 after lesion, pTracer-mNRTN-His or pGreenLantern-1 plasmids were intranigrally transfected using the NTS-polyplex nanoparticles system. We showed that the transgenic expression in dopaminergic neurons remained until the end of the study (12 weeks). Only animals expressing NRTN-His showed recovery of tyrosine hydroxylase (TH)+ cells (28 ± 2%), their neurites (32 ± 2%) and the neuron-specific cytoskeletal marker β-III-tubulin in the substantia nigra; striatal TH(+) fibers were also recovered (52 ± 3%), when compared to the healthy condition. Neurotensin receptor type 1 levels were also significantly recovered in the substantia nigra and striatum. Dopamine recovery was 70 ± 4% in the striatum and complete in the substantia nigra. The number of dendritic spines of striatal medium spiny neurons was also significantly increased, but the recovery was not complete. Drug-activated circling behavior decreased by 73 ± 2% (methamphetamine) and 89 ± 1% (apomorphine). Similar decrease was observed in the spontaneous motor behavior. Our results demonstrate that NRTN causes presynaptic and postsynaptic restoration of the nigrostriatal dopaminergic system after a 6-OHDA-induced chronic lesion. However, those improvements did not reach the healthy condition, suggesting that NRTN exerts lesser neurotrophic effects than other neurotrophic approaches.

Objectives: Progestins, notably progesterone (P4) and 17 alpha hydroxyprogesterone caproate, are presently used to treat pregnant women at risk of preterm birth. The aim of this study was to assess the optimal treatment options for progesterone (P4) to delay delivery using a sensitive bioassay for progesterone., Study Design: Pregnant rats, known to be highly sensitive to progestins, were treated with P4, including Prochieve ® (also known as Crinone ® ), in various vehicles from day 13 of gestation and in late gestation, days 19 to 22, and delivery times noted. Various routes of administration of P4 and various treatment periods were studied., Results: Use of micronized P4 by rectal, subcutaneous injection (sc) and topical (transdermal) administration in various oils all significantly (P<0.05-<0.001) delay delivery, but vaginal Prochieve ® did not. Administration of P4 in late gestation also prevented (P<0.001) delivery even when given 8h before delivery., Conclusions: Prochieve ® possesses little biological activity to suppress delivery in a sensitive bioassay system and suggests that this preparation may be of little value in prevention and inhibition of preterm birth. Further, this study shows: 1) Inhibition of delivery is increased with P4 treatments when given subcutaneously or topically. 2) P4 in fish oil provides the best vehicle for topical treatment and may be an effective treatment of preterm birth. 3) P4 in fish oil also delays delivery even when treatment begins just prior to normal delivery. 4) To prevent preterm birth in pregnant women, randomized controlled studies are needed with a potent progestin using better formulations and routes of administration., (Copyright © 2017. Published by Elsevier B.V.)

Background: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, wherein late diagnosis and treatment leads to deformities and disability., Objective: The aim of the study was to assess and describe the clinical and immunological characteristics, activity status of the disease, and functional capacity in a cohort of Ecuadorian patients with RA., Methods: This is a cross-sectional, descriptive study conducted on a population of patients with prediagnosed RA from public and private Ecuadorian rheumatology clinics. This study investigated 400 patients with a mean age of 50 years, 353 (82.25%) of which were female., Results: The study showed that 44.3%, 83.5%, 60.3%, 41.8%, 37.5%, and 11.5% had an acute onset of the disease, symmetrical polyarthritis, morning stiffness exceeding 1 h, dry eyes, dry mouth, and rheumatoid nodules, respectively. A total of 89.7% presented with positive rheumatoid factor, and 96.5% were anti-citrullinated protein antibody positive., Conclusion: This is the largest Ecuadorian cohort of patients with RA; clinical features are similar to those of other Latin American populations., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Microbes drive ecosystem functioning and their viruses modulate these impacts through mortality, gene transfer and metabolic reprogramming. Despite the importance of virus-host interactions and likely variable infection efficiencies of individual phages across hosts, such variability is seldom quantified. Here, we quantify infection efficiencies of 38 phages against 19 host strains in aquatic Cellulophaga (Bacteroidetes) phage-host model systems. Binary data revealed that some phages infected only one strain while others infected 17, whereas quantitative data revealed that efficiency of infection could vary 10 orders of magnitude, even among phages within one population. This provides a baseline for understanding and modeling intrapopulation host range variation. Genera specific host ranges were also informative. For example, the Cellulophaga Microviridae, showed a markedly broader intra-species host range than previously observed in Escherichia coli systems. Further, one phage genus, Cba41, was examined to investigate nonheritable changes in plating efficiency and burst size that depended on which host strain it most recently infected. While consistent with host modification of phage DNA, no differences in nucleotide sequence or DNA modifications were detected, leaving the observation repeatable, but the mechanism unresolved. Overall, this study highlights the importance of quantitatively considering replication variations in studies of phage-host interactions., (© 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Obesity is a worldwide health problem that has reached epidemic proportions. To ameliorate this problem, one approach is the use of appetite suppressants. These compounds are frequently amphetamine congeners such as diethylpropion (DEP), phentermine (PHEN), and bupropion (BUP), whose effects are mediated through serotonin, norepinephrine, and dopaminergic pathways. The nucleus accumbens (NAc) shell receives dopaminergic inputs and is involved in feeding and motor activity. However, little is known about how appetite suppressants modulate its activity. Therefore, we characterized behavioral and neuronal NAc shell responses to short-term treatments of DEP, PHEN, and BUP. These compounds caused a transient decrease in weight and food intake while increasing locomotion, stereotypy, and insomnia. They evoked a large inhibitory imbalance in NAc shell spiking activity that correlated with the onset of locomotion and stereotypy. Analysis of the local field potentials (LFPs) showed that all three drugs modulated beta, theta, and delta oscillations. These oscillations do not reflect an aversive-malaise brain state, as ascertained from taste aversion experiments, but tracked both the initial decrease in weight and food intake and the subsequent tolerance to these drugs. Importantly, the appetite suppressant-induced weight loss and locomotion were markedly reduced by intragastric (and intra-NAc shell) infusions of dopamine antagonists SCH-23390 (D1 receptor) or raclopride (D2 receptor). Furthermore, both antagonists attenuated appetite suppressant-induced LFP oscillations and partially restored the imbalance in NAc shell activity. These data reveal that appetite suppressant-induced behavioral and neuronal activity recorded in the NAc shell depend, to various extents, on dopaminergic activation and thus point to an important role for D1/D2-like receptors (in the NAc shell) in the mechanism of action for these anorexic compounds., (Copyright © 2015 the American Physiological Society.)

Introduction: Intracranial fat migration following autologous fat graft and placement of a lumbar drain for cerebrospinal fluid leak after pineal cyst resection surgery has not been previously reported., Case Presentation: The authors present a case of a 39-year-old male with a history of headaches who presented for removal of a pineal cyst from the pineal region. He subsequently experienced cerebrospinal fluid leak and postoperative Escherichia coli (E. Coli) wound infection, and meningitis, which were treated initially with wound washout and antibiotics in addition to bone removal and primary repair with primary suture-closure of the durotomy. A lumbar drain was left in place. The cerebrospinal fluid leak returned two weeks following removal of the lumbar drain; therefore, autologous fat graft repair and lumbar drain placement were performed. Three days later, the patient began experiencing right homonymous hemianopia and was found via computed tomography and magnetic resonance imaging to have autologous fat in the infra‑ and supratentorial space, including intraparenchymal and subarachnoid spread. Symptoms began to resolve with supportive care over 48 hours and had almost fully resolved within one week., Discussion: This is the first known report of a patient with an autologous fat graft entering the subarachnoid space, intraparenchymal space, and ventricles following fat graft and lumbar drainage., Conclusion: This case highlights the importance of monitoring for complications of lumbar drain placement., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study analysed the frequency of anterior uveitis (AU) and its correlations in a large cohort of patients with spondyloarthritis (SpA)., Methods: A common protocol of investigation was prospectively applied to 2012 SpA patients in 85 centres from 10 Ibero-American countries. Clinical and demographic variables and disease indexes were investigated. Categorical variables were compared by χ2 and Fisher's exact test, and continuous variables were compared by ANOVA or Kruskal-Wallis test. A value of p<0.05 was considered significant., Results: AU was referred by 372 SpA patients (18.5%). AU was statistically associated with inflammatory low back pain (p<0.001), radiographic sacroiliitis (p<0.001), enthesopathies (p=0.004), urethritis/acute diarrhoea (p<0.001), balanitis (p=0.002), hip involvement (p=0.002), HLA-B27 (p=0.003), and higher C-reactive protein (p=0.001), whilst it was negatively associated with the number of painful (p=0.03) and swollen (p=0.005) peripheral joints, psoriatic arthritis (p<0.001), psoriasis (p<0.001), nail involvement (p<0.001), and dactilitis (p=0.062; trend). No association with gender, race, and indices (disease activity, functionality and quality of life) was observed. Logistic regression showed that ankylosing spondylitis (p=0.001) and HLA-B27 (p=0.083; trend) was significantly associated with AU, while extra-articular manifestations (predominantly psoriasis) were negatively associated (p=0.016)., Conclusions: Anterior uveitis is a frequent extra-articular manifestation in SpA patients, positively associated with axial involvement and HLA-B27 and negatively associated with peripheral involvement and psoriatic arthritis.

Allopurinol is an inhibitor of xanthine oxidase. The aim of this work was to evaluate the efficacy of allopurinol to reverse the experimental cirrhosis induced by CCl4. Rats received CCl4 for 8 weeks, and immediately after allopurinol was administered for 4 weeks more. Allopurinol reversed all markers of liver damage and oxidative stress to normal values, restoring the metabolic capacity of the liver. Chronic injury by CCl4 induced significant overexpression of profibrogenic cytokine TGF-β, while allopurinol decreased this production and consequently decreased the collagen content. Moreover, allopurinol is capable of partially inhibiting NF-κB. These findings suggest that allopurinol is capable of reversing the cirrhosis induced by CCl4, modulating oxidative stress, TGF-β expression and NF-κB nuclear translocation., (© 2013 S. Karger AG, Basel.)

Allopurinol is an inhibitor of xanthine oxidase (XO), and XO is an enzyme that generates great amounts of reactive oxygen species. The aim of this work was to evaluate the efficacy of allopurinol to prevent experimental cirrhosis. Fibrosis and cirrhosis were induced by common bile duct ligation (BDL) for 4 weeks in rats. Animals were divided into 4 groups: sham-operated rats (SHAM); BDL group; BDL plus allopurinol (100 mg·kg⁻¹, p.o.), and SHAM plus allopurinol treatment. Alanine aminotransferase, γ-glutamyl transpeptidase, and alkaline phosphatase were increased in BDL rats but were preserved normal by allopurinol. XO activity was prevented by allopurinol; however, lipophilic and hydrophilic oxidative stress was not prevented by the drug. Allopurinol partially suppresses nuclear factor-κB (NF-κB) nuclear translocation and transforming growth factor-β (TGF-β) expression, and increased the active form of matrix metalloproteinase-13 (MMP-13). Moreover, collagen production induced by BDL was partially but significantly reduced by allopurinol. These findings suggest that allopurinol possesses a hepatoprotective effect probably by modulating proteins such as NF-κB, TGF-β, and MMP-13, helping to protect against liver damage induced by chronic cholestasis and a mechanism independent of oxidative stress.

Background: The aim of this work was to evaluate the hepatoprotective ability of allopurinol to prevent the liver injury induced by carbon tetrachloride (CCl(4))., Methods: Acute liver damage was induced with CCl(4) (4g/kg, by gavage); allopurinol (50mg/kg, by gavage) was given 1h before and 1h after CCl(4) intoxication and two daily doses for the previous three days. Cirrhosis was established by CCl(4) administration (0.4g/kg, i. p. three times a week, eight weeks); allopurinol was administered (100mg/kg, by gavage, daily) during the long-term of CCl(4) treatment. Alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GTP), xanthine oxidase (XO), lipid peroxidation, reduced and oxidized glutathione (GSH, GSSG, respectively), hydroxyproline and histopathologycal analysis were performed. Nuclear factor-κB (NF-κB), pro-inflammatory and anti-inflammatory cytokines, transforming growth factor-β (TGF-β) and metalloproteinase-13 (MMP-13) were analyzed by Western blots., Results: Acute injury increased ALT and γ-GTP activities, additionally enhanced NF-κB nuclear translocation and cytokines production such as tumor necrosis factor-α, interleukine-1β, and interleukine-6. Allopurinol partially prevented these effects, while increased interleukine-10. Acute and chronic CCl(4) treatments altered the levels of XO activity, lipid peroxidation, and GSH/GSSG ratio, while these remained within normal range with allopurinol administration. Necrosis, fibrosis and TGF-β production induced in chronic injury were partially prevented by allopurinol, interestingly, this drug induced MMP-13 activity., Conclusions: Allopurinol possesses antioxidant, anti-inflammatory and antifibrotic properties, probably by its capacity to reduce NF-κB nuclear translocation and TGF-β expression, as well as to induce MMP-13. General significance Allopurinol might be effective treatment of liver diseases., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs used primarily to treat inflammation, pain and fever. Their main mechanism of action is cyclooxygenase (COX) inhibition, and this enzyme has been linked to hepatotoxicity. The association of COX and liver injury has been, in part, due to the presence of COX-2 isoform in damaged liver and the possible induction of this enzyme by profibrotic molecules like Transforming Growth Factor-β (TGF-β). The aim of this work was to evaluate the effects of two of the most used NSAIDs, acetyl salicylic acid (ASA) and ibuprofen (IBP), on experimental liver fibrosis. We formed experimental groups of rats including vehicle and drug controls, damage induced by chronic CCl4 (0.4 g kg(-1) , i.p., three times per week, for 8 weeks) administration, and CCl4 plus ASA (100 mg kg(-1) , p.o., daily) or IBP (30 mg kg(-1) , p.o., daily). Both drugs showed important antifibrotic properties. They inhibited COX-2 activity, prevented oxidative stress measured as lipid peroxidation and glutathione content, and ASA inhibited partially and IBP totally increased TGF-β expression and collagen content. ASA and IBP prevented translocation of NFκB to the nucleus and, interestingly, ASA induced MMP-2 and MMP-13 whereas IBP induced MMP-2, MMP-9 and MMP-13. As a whole, these effects explain the beneficial effects of ASA and IBP on experimental liver fibrosis., (Copyright © 2011 John Wiley & Sons, Ltd.)

Purpose: Previous clinical observations suggested that coffee may have beneficial effects on the liver. In fact, an inverse relationship between coffee consumption and liver cirrhosis has been reported in humans. However, the causative role of coffee has not been established; therefore, the aim of this work was to study the effect of coffee in an experimental model of liver damage., Methods: In this work, cirrhosis was induced by chronic CCl(4) administration and soluble or grain coffee (SC, GC, respectively) were co-administered for 8 weeks., Results: CCl(4) administration elevated serum alkaline phosphatase and alanine aminotranspherase, liver lipid peroxidation, collagen content (fourfold) and TGF-β mRNA, and protein levels; depleted liver glycogen and reduced glutathione (GSH) content. Coffee prevented most of the changes produced by CCl(4). Histopathological analysis was in agreement with biochemical and molecular data. The best effect was produced by GC. It is worth noting that GC preserved the normal collagen content as well as the normal TGF-β mRNA and protein levels., Conclusions: Our results suggest (1) that coffee plays a causative role in preventing cirrhosis (at least experimental cirrhosis); (2) that action mechanisms are probably associated with down regulation of the profibrogenic cytokine TGF-β and to its antioxidant properties and, (3) that GC is more potent than SC. These findings suggest a beneficial effect of coffee on the liver. However, more clinical and basic studies must be performed before reaching a final recommendation.

This is a case of fungal sphenoid sinusitis in a diabetic patient with non-specific symptoms and bone erosion radiological findings in the superior and posterior sphenoid walls. Surgical treatment was performed by transnasal endoscopic approach and voriconazole orally thereafter. The histopathological study found fungus hyphal without mucosa invasion and the molecular study determined DNA to be Phialemonium curvatum, an unusual pathogen., (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Background: Transforming growth factor-beta (TGF-beta) plays a pivotal role in liver fibrosis, because it activates hepatic stellate cells, stimulating extracellular matrix deposition. Cyclooxygenase-2 (COX-2) has been associated with TGF-beta because its inhibition decreases TGF-beta expression and collagen production in some cultured cell types., Aim: The aim of this work was to evaluate the ability of celecoxib (a selective COX-2 inhibitor) to prevent and to reverse the liver fibrosis induced by CCl(4)., Methods: We established experimental groups of rats including vehicle and drug controls, damage induced by chronic CCl(4) administration and CCl(4) plus pharmacological treatment in both prevention and reversion models. We determined: alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, COX and metalloproteinase-2 and -9 activities, lipid peroxidation, glutathione levels, glycogen and collagen content and TGF-beta expression., Results: Celecoxib prevented and aided to the recovery of livers with necrotic and cholestatic damage. Celecoxib exhibited anti-oxidant properties by restoring the redox equilibrium (lipid peroxidation and glutathione levels). Glycogen was decreased by CCl(4), while celecoxib partially prevented and reversed this effect. Celecoxib inhibited COX-2 activity, decreased TGF-beta expression, induced metalloproteinase-2 activity and, consequently, prevented and reversed collagen accumulation., Conclusion: Our findings indicate that celecoxib exerts strong antifibrogenic and fibrolytic effects in the CCl(4) model of cirrhosis.

Dry plasma etching is a promising technique for crystalline silicon surface texturing aimed at improving solar cell efficiencies by reducing incident light reflection and backscattering at the cell front surface. In this work we present a new optical characterization technique for textured surfaces based on a Mueller polarimeter coupled with a high numerical aperture microscope operated either in real or in angular spaces. This tool provides both the specularly reflected and the angle-resolved backscattered intensities in a very efficient manner, due to the absence of moving parts. Three different silicon samples were etched in a standard reactor with SF(6)/O(2) plasmas at various RF powers, resulting in different textures that were characterized by scanning electron microscopy, standard reflectometry, and by our tool. The three techniques yielded consistent results. However, reflectometry could not take into account the backscattered light from highly textured surfaces, leading to significant underestimation of the overall amount of the reflected light. In contrast, our tool has demonstrated the potential to measure both reflected and backscattered light quickly and efficiently for all samples, paving the way for a new characterization technique for textured solar cells both at the development and at the production stage.

Objectives: N-acetylcysteine (NAC) is an antioxidant, a precursor of reduced glutathione, and an inhibitor of the profibrotic cytokine liver transforming growth factor-beta (TGF-beta). Carbon tetrachloride (CCl4) cirrhosis is characterized by oxidative stress and fibrosis. Therefore, the aim of this work was to study the effect of NAC on experimental cirrhosis., Methods: CCl4 was chronically administered for 8 weeks along with 300 mg/kg of NAC orally once a day. Alkaline phosphatase, alanine aminotransferase, and gamma-glutamyltranspeptidase were measured in plasma. Hydroxyproline, glycogen, lipid peroxidation, glutathione were determined in liver samples by colorimetric methods. TGF-beta was evaluated by western blotting, and a histopathological analysis was performed., Results: Serum markers of liver damage increased by CCl4 intoxication (P<0.05), whereas cotreatment with NAC prevented these increases (P<0.05); glycogen was depleted in the cirrhotic group (P<0.05), but preserved by NAC (P<0.05). Lipid peroxidation increased and glutathione decreased by the administration of CCl4 (P<0.05), again NAC prevented both effects (P<0.05). Importantly, collagen increased by about seven-fold in the CCl4 group (P<0.05); administration of NAC preserved the normal levels of collagen (P<0.05). Biochemical determinations were corroborated by hematoxylin and eosin, and trichromic stains. Western blots revealed a four-fold increase in TGF-beta in the group receiving CCl4, NAC cotreatment abolished TGF-beta signal (P<0.05)., Conclusion: Our results strongly suggest that NAC prevents experimental cirrhosis by two mechanisms: by preventing oxidative stress and by downregulating the profibrogenic cytokine TGF-beta. As NAC is currently used in humans intoxicated with paracetamol, it can be tested in fibrotic or cirrhotic patients under controlled trials.

Liver fibrosis is characterized by an excess of collagen fiber deposition, and it is known that Kupffer cells play an important role by immunomodulation of the toxic response. Methyl palmitate (MP) is an effective Kupffer cell inhibitor. The aim of this work was to evaluate the effect of MP on experimental liver fibrosis. Four groups were formed: the control group, which received the vehicles only; CCl(4) group (0.4 g kg(-1), i.p., three times a week, for eight weeks); CCl(4) plus MP (300 mg kg(-1), i.p., daily); and MP alone. Alanine aminotransferase was increased by CCl(4), and MP did not prevent this increase. Lipid peroxidation was increased markedly by CCl(4); again, MP was not able to prevent this effect. Fibrosis increased nearly 6-fold (measured as liver hydroxyproline content) in the CCl(4) group; MP preserved the normal content of collagen. These results were corroborated by histopathology. To elucidate the antifibrogenic mechanism of MP, we measured the production of TGF-beta; CCl(4) increased this cytokine several-fold, and MP abolished this increase. Collectively the present results indicate that MP possesses a strong antifibrogenic effect at least in the CCl(4) model of fibrosis. The antifibrotic effect of MP is probably associated with its ability to reduce TGF-beta content, maybe by immunomodulation of Kupffer cells functioning.