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The article presents the outcomes of a monitoring campaign and a survey performed in a~school building in Tirana. Included in the Bilateral Agreement between the National Research Council of Italy and the Ministry of Education and Sport of the Republic of Albania, the research is based on environmental analysis, collection of data from monitoring of environmental variables and students' feedback. The monitoring of Indoor Environmental Quality (IEQ) was carried out with a~nearable Environmental Monitoring System (nEMoS) for IEQ purposes, designed and developed by ITC-CNR based on the Do-It-Yourself (DIY) philosophy. The proliferation of the maker movement philosophy has promoted the diffusion of DIY-based technologies. The spread of this movement is observed outside schools but there is a growing interest among educators to introduce this philosophy in the students' education, approaching to STEAM (Science Technology Engineering Arts Mathematics) in a different and more stimulating way. The application of two nEMoS devices in two classrooms (in different locations) aroused the curiosity of students, bringing them closer to the world of technology with a practical example. It also increased their awareness about the overall IEQ conditions in the classrooms where they spend a considerable part of their lives.

Since its introduction in 2010, the nearly Zero Energy Building (nZEB) concept has known a large diffusion in European countries. Albania, an aspiring candidate country to join the European Union EU, is paving the way towards its introduction by transposing EU directives in the fields of energy efficiency into the national legislation. Most of the national building stock includes buildings with low thermal and energy performance but with high refurbishment potential, too. The country can become an important contributor in the EU decarbonization strategy due to the high percentage of electricity produced by hydropower stations, making it one of the least carbon-intensity countries in the electricity production point of view. The article focuses on the evaluation of the energy performance of an existing school located in Tirana and the potentialities to reach the nZEB target, analysing both the suitable technological solutions and the energy market situation. The Primary Energy Factors PEF for the local electricity market are estimated referring to statistical data and in comparison, with neighbouring countries, Italy and Greece, in order to investigate the potential of the achievement of the nZEB target in Albania.

The article describes the outcomes of the monitoring campaign carried out in an educational building nearby Tirana, capital of Albania. Performed under the bilateral agreement between the National Research Council of Italy and the Ministry of Education and Sport of the Republic of Albania, the study proposes a combined approach for the assessment of the IEQ, not limiting only in the collection of objective data through the environmental monitoring of indoor variables but it also includes the subjective perception of indoor environment by the students through the compilation of a specific questionnaire. The classrooms were also modelled using a parametric model combining the functionalities of Honeybee plugin with OpenStudio and Radiance. The results are illustrated by maps of the indoor microclimate and illuminance with spatial resolution of 0.5 meters and one-hour temporal resolution step. Aggregated index and environmental data derived from models are compared to those monitored with nEMoS. This hybrid method overcomes the drawback caused by a low resolution of the monitoring steps and allows the comparison of the objective and subjective perception of the considered environmental factors, as well as the identification of discrepancies in terms of objective evidence and subjective perception related to the considered environmental factors.

The quality of the indoor environment, in terms of thermal, lighting, air and acoustic quality, grouped in the Indoor Environmental Quality (IEQ) concept, plays a key role in occupants’ wellbeing and satisfaction. Only in recent years IEQ has been investigated as a whole. Today, IEQ occupies the same place of energy efficiency in the design of buildings, especially those with high performance level as the Zero-Energy Buildings (ZEB). The research deals with an experimental campaign during the cooling season carried out in a ZEB laboratory that involved 100 participants aimed at evaluating the IEQ and the indoor environments (e.g. thermal and air quality). The test consists in a survey, during which each participant is required to answer a questionnaire about how he feels the indoor environment. The experimental campaign was completed with a monitoring activity aimed at detecting the main environmental variables that can affect the participants’ answers. Collected data were treated with regression techniques to highlight possible relationships between them. The results show how in a building with high levels of energy performances the air quality plays a key role on occupants’ evaluation.

Personal Thermal Comfort models differ from the steady-state methods because they consider personal user feedback as target value. Today, the availability of integrated “smart” devices following the concept of the Internet of Things and Machine Learning (ML) techniques allows developing frameworks reaching optimized indoor thermal comfort conditions. The article investigates the potential of such approach through an experimental campaign in a test cell, involving 25 participants in a Real (R) and Virtual (VR) scenario, aiming at evaluating the effect of external stimuli on personal thermal perception, such as the variation of colours and images of the environment. A dataset with environmental parameters, biometric data and the perceived comfort feedbacks of the participants is defined and managed with ML algorithms in order to identify the most suitable one and the most influential variables that can be used to predict the Personal Thermal Comfort Perception (PTCP). The results identify the Extra Trees classifier as the best algorithm. In both R and VR scenario a different group of variables allows predicting PTCP with high accuracy.

Abstract Background Cardiovascular diseases (CVD) in diabetic patients have endothelial dysfunction as a key pathogenetic event. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), plays a pivotal role in endothelial dysfunction. Different natural polyphenols have been shown to preserve endothelial function and prevent CVD. In this study, we assessed the effect of silibinin, a widely used flavonolignan from milk thistle, on ADMA levels and endothelial dysfunction in db/db mice. Methods Eight-week-old db/db mice were administrated a 20 mg/Kg i.p. daily dose of silibinin (n = 6) or vehicle (n = 6) for four weeks. Heterozygous lean db/m mice served as control. Plasma, aorta and liver ADMA levels were determined by ELISA. Vascular reactivity to phenilephrine (PE), acetylcholine (ACh), sodium nitroprusside (SNP) and ADMA was assessed in isolated aortic segments, in wire myograph. Results Plasma and aorta ADMA levels were higher in db/db than in control lean mice. Silibinin administration markedly decreased plasma ADMA; consistently, aorta ADMA was reduced in silibinin-treated animals. Plasma and aorta ADMA levels exhibited a positive correlation, whereas liver ADMA was inversely correlated with both plasma and aorta ADMA concentrations. Endothelium-(NO)-dependent vasodilatation to ACh was impaired in db/db mice and was restored in the silibinin group, in accordance with the observed reduction of plasma and vascular levels of ADMA. Endothelium-independent vasodilatation to SNP was not modified by silibinin administration; contractile tone induced in isolated aorta from db/db mice by challenging with exogenous ADMA was not affected by the treatment. Conclusions Silibinin markedly improves endothelial dysfunction in db/db mice by reducing circulating and vascular ADMA levels. Clinical studies are warranted to assess the efficacy of silibinin for cardiovascular protection.

Sage ( Salvia officinalis L.) is a medicinal and aromatic plant (MAP) belonging to the Lamiaceae family. Its morphological, productive and chemical characteristics are affected by abiotic and biotic factors. The use of biostimulants seems to be one of the most interesting innovative practices due to fact they can represent a promising approach for achieving sustainable and organic agriculture. Despite a large application in horticulture, the use of biostimulants on MAPs has been poorly investigated. On this basis, a field experiment in a 2-year study was done to assess the effect of foliar treatments with different types of biostimulants (containing seaweeds, fulvic acids and protein hydrolysates) and two frequencies of application on morphological, productive, and chemical characteristics of S. officinalis grown organically in Mediterranean environment. Morphological, productive, and chemical parameters were affected by the factors. The biostimulant application generated higher plant height, chlorophyll content, relative water content, biomass yield and essential oil yield compared to control plants. In addition, more frequent application of biostimulants produced higher biomass and essential oil yield. The application of fulvic acid and protein hydrolysates every week produced the highest total fresh yields (between 3.9 and 8.7 t ha -1 ) and total dry yields (between 1.3 and 2.5 t ha -1 ). The essential oil yield almost doubled (33.9 kg ha -1 ) with a higher frequency of protein hydrolysates application. In this study, 44 essential oil compounds were identified, and the frequency factor significantly influenced the percentage of 38 compounds. The highest percentage of some of the most representative monoterpenes, such as 1,8-cineole, α-thujone and camphor, were observed in biostimulated plants, with average increases between 6% and 35% compared to control plants. The highest values for total phenolics, rosmarinic acid, antioxidant activity were obtained in control plants and with a lower frequency of biostimulant applications. This study emphasizes how biostimulant applications may be used to improve sage production performance and essential oil parameters when produced in agricultural organic system. At the same time, biostimulants application caused a decrease in total phenolic, antioxidant activity and rosmarinic acid values., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Farruggia, Di Miceli, Licata, Leto, Salamone and Novak.)

Rapeseed ( Brassica napus var. oleifera D.C.) and Ethiopian mustard ( Brassica carinata A. Braun) are promising industrial crops for cultivation in the Southern Mediterranean area due to profitable yields under semi-arid conditions. The exploitation of raw materials produced by these crops is very convenient for farmers to produce bioenergy directly on-farm and permits them to create a short agri-energy supply chain. The purpose of this study was to determine their yield performance under rainfed conditions and make an economic assessment of a combined heat and power plant (CHP) system operating on pure vegetable oil (PVO). Tests were conducted in Sicily (Italy) from 2012 to 2014. Seed and crop residue yields were detected. The analysis of seed, defatted seed meal and crop residue, and the chemical-physical aspects of PVO were carried out according to conventional protocols. A pilot CHP system was used for cogenerating electricity and heat. In general, rapeseed had the highest seed (2.27 t ha -1 ) and oil (1.11 t ha -1 ) yields. The average oil content ranged from 44.88 % (Ethiopian mustard) to 45.73 % dry matter (rapeseed). Ethiopian mustard performed better than rapeseed in terms of aboveground biomass yield (5.49 t ha -1 ), in both years. The two crops showed different fatty acid profiles of the oil mainly due to diverse content of erucic and oleic acids. The CHP system had an average consumption of 14.41 kg PVO h -1 . These results confirm that the productivity of the species can be appreciable in the Southern Mediterranean area and indicate the use of raw materials of these crops as crucial to the development a sustainable short agri-energy supply chain., Competing Interests: 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., (© 2024 The Authors. Published by Elsevier Ltd.)

The vegetative propagation of hops, despite being a reliable method, is not very common due to the unavailability of the plant material. In this study, the technique of in vitro propagation was applied to the Cascade variety of Humulus lupulus L. The plant material was collected from a private field in Sicily; the explants were subjected to sterilization before in vitro culture. Single-node explants were placed in in vitro culture in nine different culture media for multiplication. Thidiazuron (TDZ), Benzyladenine (BAP) and meta-Topoline (mT) were tested for multiplication phase. For the rooting phase, five types of different culture media were evaluated. Binodal cuttings coming from the previous multiplication test were placed in the culture. The rooting media differ from each other in the concentration and ratio of two auxin hormones: Indolo-3-acetic acid (IAA) and Indole-3-butyric acid (IBA). In vitro rooted plants obtained from the rooting phase were transferred to ex vitro conditions in a microbox with agri-perlite and a solution containing Murashige and Skoog (MS) basal medium at half concentration. With a culture medium containing the highest TDZ doses (H6) and combination with cytokinin (H8 and H9), the highest shoot percentage was obtained. After 3 months of in vitro culture, the highest shoot percentage was observed in the culture medium with 2 mL L -1 of BAP. The highest rooting percentage, roots numbers and root length were found when the culture medium was supplemented with 1 mL L -1 of IAA. The usage of agri-perlite and MS at half concentration, without PGR, allowed us to obtain a 99.1% survival rate. This micropropagation protocol is useful for obtaining virus-free plants and for the development of the brewery industry.

The Asparagus genus includes approximately 240 species, the most important of which is garden asparagus ( Asparagus officinalis L.), as this is a vegetable crop cultivated worldwide for its edible spear. Along with garden asparagus, other species are also cultivated (e.g., Asparagus maritimus L.) or have been proposed as untapped sources of variability in breeding programs (e.g., Asparagus acutifolius L.). In the present work, we applied reduced-representation sequencing to examine a panel of 378 diverse asparagus genotypes, including commercial hybrids, interspecific lines, wild relatives of garden asparagus, and doubled haploids currently used in breeding programs, which enabled the identification of more than 200K single-nucleotide polymorphisms (SNPs). These SNPs were used to assess the extent of linkage disequilibrium in the diploid gene pool of asparagus and combined with preliminary phenotypic information to conduct genome-wide association studies for sex and traits tied to spear quality and production. Moreover, using the same phenotypic and genotypic information, we fitted and cross-validated genome-enabled prediction models for the same set of traits. Overall, our analyses demonstrated that, unlike the diversity detected in wild species related to garden asparagus and in interspecific crosses, cultivated and wild genotypes of A. officinalis L. show a narrow genetic basis, which is a contributing factor hampering the genetic improvement of this crop. Estimating the extent of linkage disequilibrium and providing the first example of genome-wide association study and genome-enabled prediction in this species, we concluded that the asparagus panel examined in the present study can lay the foundation for determination of the genetic bases of agronomically important traits and for the implementation of predictive breeding tools to sustain breeding., 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 © 2023 Sala, Puglisi, Ferrari, Salamone, Tassone, Rotino, Fricano and Losa.)

Ubiquitous computing has enabled the proliferation of low-cost solutions for capturing information about the user's environment or biometric parameters. In this sense, the do-it-yourself (DIY) approach to build new low-cost systems or verify the correspondence of low-cost systems compared to professional devices allows the spread of application possibilities. Following this trend, the authors aim to present a complete DIY and replicable procedure to evaluate the performance of a low-cost video luminance meter consisting of a Raspberry Pi and a camera module. The method initially consists of designing and developing a LED panel and a light cube that serves as reference illuminance sources. The luminance distribution along the two reference light sources is determined using a Konica Minolta luminance meter. With this approach, it is possible to identify an area for each light source with an almost equal luminance value. By applying a frame that covers part of the panel and shows only the area with nearly homogeneous luminance values and applying the two systems in a dark space in front of the low-cost video luminance meter mounted on a professional reference camera photometer LMK mobile air, it is possible to check the discrepancy in luminance values between the low-cost and professional systems when pointing different homogeneous light sources. In doing so, we primarily consider the peripheral shading effect, better known as the vignetting effect. We then differentiate the correction factor S of the Radiance Pcomb function to better match the luminance values of the low-cost system to the professional device. We also introduce an algorithm to differentiate the S factor depending on the light source. In general, the DIY calibration process described in the paper is time-consuming. However, the subsequent applications in various real-life scenarios allow us to verify the satisfactory performance of the low-cost system in terms of luminance mapping and glare evaluation compared to a professional device.

The so-called Internet of Things (IoT), which is rapidly increasing the number of network-connected and interconnected objects, could have a far-reaching impact in identifying the link between human health, well-being, and environmental concerns. In line with the IoT concept, many commercial wearables have been introduced in recent years, which differ from the usual devices in that they use the term "smart" alongside the terms "watches", "glasses", and "jewellery". Commercially available wearables aim to enhance smartphone functionality by enabling payment for commercial items or monitoring physical activity. However, what is the trend of scientific production about the concept of wearables regarding environmental monitoring issues? What are the main areas of interest covered by scientific production? What are the main findings and limitations of the developed solution in this field? The methodology used to answer the above questions is based on a systematic review. The data were acquired following a reproducible methodology. The main result is that, among the thermal, visual, acoustic, and air quality environmental factors, the last one is the most considered when using wearables even though in combination with some others. Another relevant finding is that of the acquired studies; in only one, the authors shared their wearables as an open-source device, and it will probably be necessary to encourage researchers to consider open-source as a means to promote scalability and proliferation of new wearables customized to cover different domains.

Users' satisfaction in indoor spaces plays a key role in building design. In recent years, scientific research has focused more and more on the effects produced by the presence of greenery solutions in indoor environments. In this study, the Internet of Things (IoT) concept is used to define an effective solution to monitor indoor environmental parameters, along with the biometric data of users involved in an experimental campaign conducted in a Zero Energy Building laboratory where a living wall has been installed. The growing interest in the key theory of the IoT allows for the development of promising frameworks used to create datasets usually managed with Machine Learning (ML) approaches. Following this tendency, the dataset derived by the proposed infield research has been managed with different ML algorithms in order to identify the most suitable model and influential variables, among the environmental and biometric ones, that can be used to identify the plant configuration. The obtained results highlight how the eXtreme Gradient Boosting (XGBoost)-based model can obtain the best average accuracy score to predict the plant configuration considering both a selection of environmental parameters and biometric data as input values. Moreover, the XGBoost model has been used to identify the users with the highest accuracy considering a combination of picked biometric and environmental features. Finally, a new Green View Factor index has been introduced to characterize how greenery has an impact on the indoor space and it can be used to compare different studies where green elements have been used.

Personal Thermal Comfort models consider personal user feedback as a target value. The growing development of integrated "smart" devices following the concept of the Internet of Things and data-processing algorithms based on Machine Learning techniques allows developing promising frameworks to reach the best level of indoor thermal comfort closest to the real needs of users. The article investigates the potential of a new approach aiming at evaluating the effect of visual stimuli on personal thermal comfort perception through a comparison of 25 participants' feedback exposed to a real scenario in a test cell and the same environment reproduced in Virtual Reality. The users' biometric data and feedback about their thermal perception along with environmental parameters are collected in a dataset and managed with different Machine Learning techniques. The most suitable algorithm, among those selected, and the influential variables to predict the Personal Thermal Comfort Perception are identified. The Extra Trees classifier emerged as the most useful algorithm in this specific case. In real and virtual scenarios, the most important variables that allow predicting the target value are identified with an average accuracy higher than 0.99.

Thermal comfort has become a topic issue in building performance assessment as well as energy efficiency. Three methods are mainly recognized for its assessment. Two of them based on standardized methodologies, face the problem by considering the indoor environment in steady-state conditions (PMV and PPD) and users as active subjects whose thermal perception is influenced by outdoor climatic conditions (adaptive approach). The latter method is the starting point to investigate thermal comfort from an overall perspective by considering endogenous variables besides the traditional physical and environmental ones. Following this perspective, the paper describes the results of an in-field investigation of thermal conditions through the use of nearable and wearable solutions, parametric models and machine learning techniques. The aim of the research is the exploration of the reliability of IoT-based solutions combined with advanced algorithms, in order to create a replicable framework for the assessment and improvement of user thermal satisfaction. For this purpose, an experimental test in real offices was carried out involving eight workers. Parametric models are applied for the assessment of thermal comfort; IoT solutions are used to monitor the environmental variables and the users' parameters; the machine learning CART method allows to predict the users' profile and the thermal comfort perception respect to the indoor environment.

The article describes the results of the project "open source smart lamp" aimed at designing and developing a smart object able to manage and control the indoor environmental quality (IEQ) of the built environment. A first version of this smart object, built following a do-it-yourself (DIY) approach using a microcontroller, an integrated temperature and relative humidity sensor, and techniques of additive manufacturing, allows the adjustment of the indoor thermal comfort quality (ICQ), by interacting directly with the air conditioner. As is well known, the IEQ is a holistic concept including indoor air quality (IAQ), indoor lighting quality (ILQ) and acoustic comfort, besides thermal comfort. The upgrade of the smart lamp bridges the gap of the first version of the device providing the possibility of interaction with the air exchange unit and lighting system in order to get an overview of the potential of a nearable device in the management of the IEQ. The upgraded version was tested in a real office equipped with mechanical ventilation and an air conditioning system. This office was occupied by four workers. The experiment is compared with a baseline scenario and the results show how the application of the nearable device effectively optimizes both IAQ and ILQ.

nEMoS (nano Environmental Monitoring System) is a 3D-printed device built following the Do-It-Yourself (DIY) approach. It can be connected to the web and it can be used to assess indoor environmental quality (IEQ). It is built using some low-cost sensors connected to an Arduino microcontroller board. The device is assembled in a small-sized case and both thermohygrometric sensors used to measure the air temperature and relative humidity, and the globe thermometer used to measure the radiant temperature, can be subject to thermal effects due to overheating of some nearby components. A thermographic analysis was made to rule out this possibility. The paper shows how the pervasive technique of additive manufacturing can be combined with the more traditional thermographic techniques to redesign the case and to verify the accuracy of the optimized system in order to prevent instrumental systematic errors in terms of the difference between experimental and actual values of the above-mentioned environmental parameters.

The article describes the design phase, development and practical application of a smart object integrated in a desk lamp and called "Smart Lamp", useful to optimize the indoor thermal comfort and energy savings that are two important workplace issues where the comfort of the workers and the consumption of the building strongly affect the economic balance of a company. The Smart Lamp was built using a microcontroller, an integrated temperature and relative humidity sensor, some other modules and a 3D printer. This smart device is similar to the desk lamps that are usually found in offices but it allows one to adjust the indoor thermal comfort, by interacting directly with the air conditioner. After the construction phase, the Smart Lamp was installed in an office normally occupied by four workers to evaluate the indoor thermal comfort and the cooling consumption in summer. The results showed how the application of the Smart Lamp effectively reduced the energy consumption, optimizing the thermal comfort. The use of DIY approach combined with read-write functionality of websites, blog and social platforms, also allowed to customize, improve, share, reproduce and interconnect technologies so that anybody could use them in any occupied environment.

The article describes the design phase, development and practical application of a low-cost control system for a forced circulation solar plant in an outdoor test cell located near Milan. Such a system provides for the use of an electric pump for the circulation of heat transfer fluid connecting the solar thermal panel to the storage tank. The running plant temperatures are the fundamental parameter to evaluate the system performance such as proper operation, and the control and management system has to consider these parameters. A solar energy-powered wireless-based smart object was developed, able to monitor the running temperatures of a solar thermal system and aimed at moving beyond standard monitoring approaches to achieve a low-cost and customizable device, even in terms of installation in different environmental conditions. To this end, two types of communications were used: the first is a low-cost communication based on the ZigBee protocol used for control purposes, so that it can be customized according to specific needs, while the second is based on a Bluetooth protocol used for data display.

The Indoor Environmental Quality (IEQ) refers to the quality of the environment in relation to the health and well-being of the occupants. It is a holistic concept, which considers several categories, each related to a specific environmental parameter. This article describes a low-cost and open-source hardware architecture able to detect the indoor variables necessary for the IEQ calculation as an alternative to the traditional hardware used for this purpose. The system consists of some sensors and an Arduino board. One of the key strengths of Arduino is the possibility it affords of loading the script into the board's memory and letting it run without interfacing with computers, thus granting complete independence, portability and accuracy. Recent works have demonstrated that the cost of scientific equipment can be reduced by applying open-source principles to their design using a combination of the Arduino platform and a 3D printer. The evolution of the 3D printer has provided a new means of open design capable of accelerating self-directed development. The proposed nano Environmental Monitoring System (nEMoS) instrument is shown to have good reliability and it provides the foundation for a more critical approach to the use of professional sensors as well as for conceiving new scenarios and potential applications.

Aim: To establish if the juice of Moro, an anthocyanin-rich orange, may improve liver damage in mice with diet-induced obesity., Methods: Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk. Liver morphology, gene expression of lipid transcription factors, and metabolic enzymes were assessed., Results: Mice fed HFD displayed increased body weight, insulin resistance and dyslipidemia. Moro juice administration limited body weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and total cholesterol. Mice fed HFD showed liver steatosis associated with ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase 1 activity., Conclusion: Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

Background: Cardiovascular diseases (CVD) in diabetic patients have endothelial dysfunction as a key pathogenetic event. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), plays a pivotal role in endothelial dysfunction. Different natural polyphenols have been shown to preserve endothelial function and prevent CVD. In this study, we assessed the effect of silibinin, a widely used flavonolignan from milk thistle, on ADMA levels and endothelial dysfunction in db/db mice., Methods: Eight-week-old db/db mice were administrated a 20 mg/Kg i.p. daily dose of silibinin (n = 6) or vehicle (n = 6) for four weeks. Heterozygous lean db/m mice served as control. Plasma, aorta and liver ADMA levels were determined by ELISA. Vascular reactivity to phenilephrine (PE), acetylcholine (ACh), sodium nitroprusside (SNP) and ADMA was assessed in isolated aortic segments, in wire myograph., Results: Plasma and aorta ADMA levels were higher in db/db than in control lean mice. Silibinin administration markedly decreased plasma ADMA; consistently, aorta ADMA was reduced in silibinin-treated animals. Plasma and aorta ADMA levels exhibited a positive correlation, whereas liver ADMA was inversely correlated with both plasma and aorta ADMA concentrations. Endothelium-(NO)-dependent vasodilatation to ACh was impaired in db/db mice and was restored in the silibinin group, in accordance with the observed reduction of plasma and vascular levels of ADMA. Endothelium-independent vasodilatation to SNP was not modified by silibinin administration; contractile tone induced in isolated aorta from db/db mice by challenging with exogenous ADMA was not affected by the treatment., Conclusions: Silibinin markedly improves endothelial dysfunction in db/db mice by reducing circulating and vascular ADMA levels. Clinical studies are warranted to assess the efficacy of silibinin for cardiovascular protection.

We have previously observed a significant reduction of ceftriaxone resistance in Proteus mirabilis associated with an increase in the use of cefepime, along with a decrease in the consumption of broad-spectrum cephalosporins (CEP). However, we did not observe such a reduction with Klebsiella pneumoniae. Therefore, we sought to determine whether replacement of CEP by piperacillin-tazobactam might be useful in reducing sustained high rates of CEP resistance by this organism. We used a 6-month "before and after model"; during the second (intervention) period, most prescriptions of CEP were changed to piperacillin-tazobactam at the pharmacy. No additional barrier precautions were undertaken. During intervention, consumption of ceftazidime decreased from 17.73 to 1.14 defined daily doses (DDD) per 1,000 patient-days (P < 0.0001), whereas that of piperacillin-tazobactam increased from 0 to 30.57 DDD per 1,000 patient-days (P < 0.0001). The levels of resistance to CEP by K. pneumoniae and P. mirabilis decreased from 68.4 and 57.9% to 37.5 and 29.4%, respectively (P < 0.05). We conclude that replacement of ceftazidime by piperacillin-tazobactam might be a suitable strategy to decrease endemic CEP resistance by K. pneumoniae and P. mirabilis, even where there are high bacterial resistance rates and irrespective of any additional precautions for controlling nosocomial infection.

We describe the functional consequences of mutations in the linker between the second and third transmembrane segments (M2-M3L) of muscle acetylcholine receptors at the single-channel level. Hydrophobic mutations (Ile, Cys, and Phe) placed near the middle of the linker of the alpha subunit (alphaS269) prolong apparent openings elicited by low concentrations of acetylcholine (ACh), whereas hydrophilic mutations (Asp, Lys, and Gln) are without effect. Because the gating kinetics of the alphaS269I receptor (a congenital myasthenic syndrome mutant) in the presence of ACh are too fast, choline was used as the agonist. This revealed an approximately 92-fold increased gating equilibrium constant, which is consistent with an approximately 10-fold decreased EC(50) in the presence of ACh. With choline, this mutation accelerates channel opening approximately 28-fold, slows channel closing approximately 3-fold, but does not affect agonist binding to the closed state. These ratios suggest that, with ACh, alphaS269I acetylcholine receptors open at a rate of approximately 1.4 x 10(6) s(-1) and close at a rate of approximately 760 s(-1). These gating rate constants, together with the measured duration of apparent openings at low ACh concentrations, further suggest that ACh dissociates from the diliganded open receptor at a rate of approximately 140 s(-1). Ile mutations at positions flanking alphaS269 impair, rather than enhance, channel gating. Inserting or deleting one residue from this linker in the alpha subunit increased and decreased, respectively, the apparent open time approximately twofold. Contrary to the alphaS269I mutation, Ile mutations at equivalent positions of the beta, straightepsilon, and delta subunits do not affect apparent open-channel lifetimes. However, in beta and straightepsilon, shifting the mutation one residue to the NH(2)-terminal end enhances channel gating. The overall results indicate that this linker is a control element whose hydrophobicity determines channel gating in a position- and subunit-dependent manner. Characterization of the transition state of the gating reaction suggests that during channel opening the M2-M3L of the alpha subunit moves before the corresponding linkers of the beta and straightepsilon subunits.

1. During routine sequencing of our mouse muscle alpha subunit acetylcholine receptor channel (AChR) cDNA clones, we detected a discrepancy with the GenBank database entry (accession X03986). At nucleotides 1305-7 (residue 433, in the M4 domain) the database lists GTC which encodes a valine, while our putative 'wild-type' cDNA had the nucleotides GCC, which encodes an alanine. No other sequence differences were found. 2. PCR amplification of genomic DNA confirmed that the BALB/C mouse alpha subunit gene has a T nucleotide at position 1306, and, therefore, that the protein has a V at position 433 in the M4 segment. 3. In order to determine the functional consequences of this difference, either wild-type (V433) or mutant (A433) alpha subunits were co-expressed in HEK cells with mouse beta, epsilon and delta subunits. Single-channel currents were recorded in cell-attached patches, and rate and equilibrium constants were estimated from open and closed durations obtained from a range of ACh concentrations. No significant differences were found between the activation rate constants or equilibrium constants of the V433 and A433 variants. 4. Kinetic modelling of alphaV433 AChR suggests that the two transmitter binding sites have similar dissociation equilibrium constants for acetylcholine ( approximately 160 microM in 142 mM extracellular KCl). 5. Diliganded AChRs occupy a closed state that has a lifetime of approximately 1 ms. The rate constants for entering and leaving this state do not vary with the ACh concentration. 6. The kinetics of a mutant AChR that causes a slow channel congenital myaesthenic syndrome, alphaG153S, was re-examined. The properties of this mutant were similar with a V or an A at position alpha433.

Sulbactam/ampicillin appears to be effective in the treatment of gynecologic and intra-abdominal infections, and infections of skin and skin structures. However, until more data is available from well-controlled, comparative studies, it is difficult to determine the most appropriate place of sulbactam/ampicillin in the therapy of these and other infections. Sulbactam/ampicillin is similar to other agents in the prophylaxis of infectious complications secondary to gastrointestinal and gynecologic surgery, and may have a role in surgical prophylaxis as it is well tolerated by most patients and is cost-effective. Indeed, the discovery of sulbactam provides us with yet another useful compound. Additional study is clearly needed so as to best use sulbactam to its fullest advantage.