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RATIONALE AND OBJECTIVES: Cervical ultrasound (US) is crucial in the follow-up of differentiated thyroid cancer (DTC). However, there are no guidelines for its acquisition and documentation, particularly concerning the role of additional video sequences, known as US cine loops (UCL). The aim of this study is to examine the clinical relevance (CR) of a new Standard Operating Procedure (SOP) for cervical UCL in DTC follow-up. MATERIALS AND METHODS: A retrospective analysis was conducted on all UCL examinations of DTC follow-up patients at a tertiary care center between January 2010 and February 2018 to determine their clinical significance. The patients were divided into two groups: those with no documented CR (UCL-nCR) and those with documented CR (UCL-CR). The study reviewed the respective written medical US reports that were validated by experienced residents. The UCL-CR were categorized in: confirmation of a suspicious finding that was identified during conventional live US (UCL-CRcon), identification of a suspicious finding that was not identified during conventional live US (UCL-CRide), and invalidation of a suspicious finding that was identified during conventional live US (UCL-CRinv). RESULTS: A total of 5512 UCLs in 652 DTC patients were analyzed, with 71.5% women and a mean age of 50 years. More than 90% of the tumors were low-risk at initial staging. The mean number of UCLs per patient was 8.5 ± 4.6. Overall, 95 cases of UCL-CR were identified in 82 patients (12.6%), with a patient-based number needed to scan of 8. UCL-CRinv was the most common type of UCL-CR, accounting for 77 (81.1%) of cases. The occurrences of 12 UCL-CRcon (12.6%) and 6 UCL-CRide (6.3%) were correspondingly less frequent. The diagnosis of UCL-CR was confirmed in 91.6% of cases during the clinical course. CONCLUSIONS: In 12.6% of the patients, the additional acquisition and archiving of cervical UCL revealed clinical relevance in the course of DTC disease. The invalidation of suspicious findings through the retrospective analysis of former UCL occurred as the most significant benefit of this method. The UCL SOP can be easily and quickly integrated into the US workflow.
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Whole-body vibration (WBV) is a training modality, and it seems to be a safe and efficient exercise especially to improve different aspects of physical fitness in different populations. The protocols for WBV are still not standardized. The difficulty in comparing the data confuses the real efficacy of this instrument. Consequently, the objective of this umbrella review is to analyze the protocols previously adopted and eventually to propose a standard operating procedure for WBV training. Systematic review and meta-analysis of randomized controlled trials on WBV were searched on the electronic databases PubMed, Web of Science, and Scopus until 18 March 2024. A quality assessment of the studies included has been performed. A total of 20 studies were included in this umbrella review and frequency, magnitude, and amplitude intensity data were recorded. Detailed information about the protocols (static or dynamic exercises, barefoot or with shoes, intensity duration, weekly frequency, and vibration characteristics) was also collected. WBV presents widely different protocols. Consequently, a standard operating procedure has not been proposed for WBV training. A hypothesis of intervention was instead written in which parameters for frequency, amplitude, acceleration, and training mode were proposed.
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With advanced mass spectrometry (MS)-based proteomics, genome-scale proteome coverage can be achieved from bulk cells. However, such bulk measurement obscures cell-to-cell heterogeneity, precluding proteome profiling of single cells and small numbers of cells of interest. To address this issue, in the recent 5 years, there has been a surge of small sample preparation methods developed for robust and effective collection and processing of single cells and small numbers of cells for in-depth MS-based proteome profiling. Based on their broad accessibility, they can be categorized into two types: methods based on specific devices and those based on standard PCR tubes or multi-well plates. In this chapter, we describe the detailed protocol of our recently developed, easily adoptable, Surfactant-assisted One-Pot (SOP) sample preparation coupled with MS method termed SOP-MS for label-free single-cell and nanoscale proteomics. SOP-MS capitalizes on the combination of an MS-compatible surfactant, n-dodecyl-ß-D-maltoside (DDM), and standard low-bind PCR tube or multi-well plate for "all-in-one" one-pot sample preparation without sample transfer. With its robust and convenient features, SOP-MS can be readily implemented in any MS laboratory for single-cell and nanoscale proteomics. With further improvements in MS detection sensitivity and sample throughput, we believe that SOP-MS could open an avenue for single-cell proteomics with broad applicability in biological and biomedical research.
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Proteômica , Análise de Célula Única , Tensoativos , Proteômica/métodos , Tensoativos/química , Análise de Célula Única/métodos , Humanos , Espectrometria de Massas/métodos , Proteoma/análise , Nanotecnologia/métodos , GlucosídeosRESUMO
Non-volatile memory based on thin-film transistor is crucial for system-on-panel and flexible electronic systems. Achieving high-performance and reliable thin-film transistor (TFT) memory still remains challenging. Here, for the first time, we present a ZnO TFT memory utilizing self-assembled Au nanocrystals with a low thermal budget, exhibiting excellent memory performance, including a program/erase window of 9.8 V, 29% charge loss extrapolated to 10 years, and remarkable endurance characteristics. Moreover, the memory exhibits favorable on-state characteristics with mobility, subthreshold swing, and current on-off ratio of 17.6 cm2V-1s-1, 0.71 V/dec, and 107, respectively. Our study shows that the fabricated TFT memory has great potential for practical applications.
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Free-space optical (FSO) communication can be subject to various types of distortion and loss as the signal propagates through non-uniform media. In experiment and simulation, we demonstrate that the state of polarization and degree of polarization of light passed though underwater bubbles, causing turbulence, is preserved. Our experimental setup serves as an efficient, low cost alternative approach to long distance atmospheric or underwater testing. We compare our experimental results with those of simulations, in which we model underwater bubbles, and separately, atmospheric turbulence. Our findings suggest potential improvements in polarization based FSO communication schemes.
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Sb(III) and As(III) share similar chemical features and coexist in the environment. However, their oxidase enzymes have completely different sequences and structures. This raises an intriguing question: Could Sb(III)-oxidizing prokaryotes (SOPs) also oxidize As(III), and vice versa? Regarding this issue, previous investigations have yielded unclear, incorrect and even conflicting data. This work aims to address this matter. First, we prepared an enriched population of SOPs that comprises 55 different AnoA genes, lacking AioAB and ArxAB genes. We found that these SOPs can oxidize both Sb(III) and As(III) with comparable capabilities. To further confirm this finding, we isolated three cultivable SOP strains that have AnoA gene, but lack AioAB and ArxAB genes. We observed that they also oxidize both Sb(III) and As(III) under both anaerobic and aerobic conditions. Secondly, we obtained an enriched population of As(III)-oxidizing prokaryotes (AOPs) from As-contaminated soils, which comprises 69 different AioA genes, lacking AnoA gene. We observed that the AOP population has significant As(III)-oxidizing activities, but lack detectable Sb(III)-oxidizing activities under both aerobic and anaerobic conditions. Therefore, we convincingly show that SOPs can oxidize As(III), but AOPs cannot oxidize Sb(III). These findings clarify the previous ambiguities, confusion, errors or contradictions regarding how SOPs and AOPs oxidize each other's substrate.
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Antimônio , Oxirredução , Anaerobiose , Aerobiose , Antimônio/metabolismo , Células Procarióticas/metabolismo , Microbiologia do Solo , Bactérias/metabolismo , Bactérias/genética , Poluentes do Solo/metabolismoRESUMO
Most strategies are implemented; however, South Africa needs to evaluate and develop trauma interventions. The study aims to develop, test and validate childhood trauma exposure intervention in the Vhembe district, Limpopo province. Donabedian's structure-process-outcome model will guide the study. The study will employ multiphase mixed methods with five phases. Phase 1 will be a thorough systematic evaluation of literature on childhood trauma and exposure to violence interventions to describe existing interventions. Phase 2, stage 1: Will explore the experiences of children exposed to trauma and violence regarding their experiences of the treatment they received, using semi-structured qualitative interviews. Non-probability purposeful sampling techniques will be used to select participants. The Thoyondou Victim Empowerment's database will select participants. The researchers will conduct semi-structured and unstructured interviews with youngsters exposed to violence and trauma. Stage 2 will be a qualitative study of trauma centre managers and personnel sampled from the contact record. IPA will analyze data. Phase 3 will conceptualize Phase 1 and the empirical phase into Donabedian's SPO framework for Phase 4. Phase 4 develops the intervention using Phase 3's conceptual framework and tests and validates it.
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In low-voltage power distribution station areas (DSAs), sensor devices and communication networks are often inadequate. Therefore, the control strategies mainly used for soft open points (SOPs) based on global information in medium-voltage distribution networks are difficult to be directly applied to low-voltage DSAs. This paper proposes a novel control strategy for SOP that only requires collecting the local information of SOP and the load rate of transformers. It aims to address the issues faced of voltage violations at the end of feeders and the load rate imbalance among adjacent DSAs under the current high penetration of renewable energy sources. In this paper, first, a sensor network consisting of sensor devices located at the transformers and each port of the SOP is introduced for information collection. Then, based on the sensitivity relationship between the node voltage and the injected power, considering capacity and voltage safety constraints, the adjustable range of the active power output for each port of the SOP is derived. According to this range, the operating states of the DSAs are categorized into four scenarios. For each scenario, the adjustment amount of SOP output power is determined to achieve comprehensive regulation of terminal voltage and load rate of all DSAs interconnected by SOP. Finally, the effectiveness of the proposed strategy is verified based on a simulation model of three flexible interconnected DSAs established in MATLAB/Simulink.
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PURPOSE: With respect to the European Union 2017 amendment of the Medical Device Regulations (MDR), this overview article presents recommendations concerning medical 3D printing in oral and maxillofacial surgery (OMFS). METHODS: The MDR were screened for applicability of the rules to medical in-house 3D printing. Applicable regulations were summarized and compared to the status of medical use of 3D printing in OMFS in Germany. Recommendations were made for MDR concerning medical 3D printing. RESULTS: In-house printed models, surgical guides, and implants fall under the category of Class I-III, depending on their invasive and active properties. In-house medical 3D printing for custom-made medical devices is possible under certain prerogatives: (1) the product is not being used in another facility, (2) appropriate quality systems are applied, (3) the reason for omitting commercial products is documented, (4) information about its use is supplied to the responsible authority, (5) there is a publicly accessible declaration of origin, identification, and conformity to the MDR, (6) there are records of manufacturing site, process and performance data, (7) all products are produced according to the requirements proclaimed before, and (8) there is an evaluation of clinical use and correction of possible issues. CONCLUSION: Several aspects must be addressed for in house medical 3D printing, according to the MDR. Devising MDR related to medical 3D printing is a growing challenge. The implementation of recommendations in OMFS could help practitioners to overcome the challenges and become aware of the in-house production and application of 3D printed devices.
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Impressão Tridimensional , Cirurgia Bucal , Humanos , Cirurgia Bucal/normas , Alemanha , Procedimentos Cirúrgicos Bucais/normas , União Europeia , Legislação de Dispositivos Médicos , Modelos AnatômicosRESUMO
BACKGROUND: Senile osteoporosis (SOP) is an age-related metabolic bone disease that currently lacks specific therapeutic interventions. Thus, this study aimed to investigate the effect of Astragaloside IV (AS-IV) on macrophage senescence, bone marrow mesenchymal stem cell (BMSC) osteogenesis, and SOP progression. METHODS: A senescent macrophage model was established and treated with varying concentrations of AS-IV. Cell activity was measured using the CCK8 assay. The senescence levels of macrophages were evaluated through ß-galactosidase staining, PCR, and immunofluorescence. Macrophage mitochondrial function was assessed using ROS and JC-1 staining. Macrophage polarization was evaluated through PCR, Western blot, and immunofluorescence. The inhibitory effects of AS-IV on macrophage senescence were investigated using Western blot analysis. Furthermore, the effects of macrophage conditioned medium (CM) on BMSCs osteogenic were detected using ALP, alizarin red, and PCR. RESULTS: AS-IV inhibited macrophage senescence and M1 polarization, alleviated mitochondrial dysfunction, and promoted M2 polarization. Mechanistically, it suppressed the STING/NF-κB pathway in H2O2-activated macrophages. Conversely, the STING agonist c-di-GMP reversed the effects of AS-IV on macrophage senescence. Additionally, AS-IV-induced macrophage CM promoted BMSC osteogenic differentiation. In vivo, AS-IV treatment ameliorated aberrant bone microstructure and bone mass loss in the SOP mouse model, inhibited macrophage senescence, and promoted M2 polarization. CONCLUSIONS: By modulating the STING/NF-κB signaling pathway, AS-IV potentially inhibited macrophage senescence and stimulated osteogenic differentiation of BMSCs, thus exerting an anti-osteoporotic effect. Consequently, AS-IV may serve as an effective therapeutic candidate for the treatment of osteoporosis.
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Doenças Ósseas Metabólicas , Osteoporose , Saponinas , Triterpenos , Camundongos , Animais , NF-kappa B , Osteogênese , Galactose , Peróxido de Hidrogênio/farmacologia , Diferenciação Celular , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , MacrófagosRESUMO
Sb and As are chemically similar, but the sequences and structures of Sb(III) and As(III) oxidase are totally distinct. It is thus interesting to explore whether Sb(III) oxidase oxidizes As(III), and if so, how microbial oxidations of Sb(III) and As(III) influence one another. Previous investigations have yielded ambiguous or even erroneous conclusions. This study aimed to clarify this issue. Firstly, we prepared a consortium of Sb(III)-oxidizing prokaryotes (SOPs) by enrichment cultivation. Metagenomic analysis reveals that SOPs with the Sb(III) oxidase gene, but lacking the As(III) oxidase gene are predominant in the SOP community. Despite this, SOPs exhibit comparable Sb(III) and As(III)-oxidizing activities in both aerobic and anaerobic conditions, indicating that at the microbial community level, Sb(III) oxidase can oxidize As(III). Secondly, we isolated a representative cultivable SOP, Ralstonia sp. SbOX with Sb(III) oxidase gene but without As(III) oxidase gene. Genomic analysis of SbOX reveals that this SOP strain has a complete Sb(III) oxidase (AnoA) gene, but lacks As(III) oxidase (AioAB or ArxAB) gene. It is interesting to discover that, besides its Sb(III) oxidation activities, SbOX also exhibits significant capabilities in oxidizing As(III) under both aerobic and anaerobic conditions. Moreover, under aerobic conditions and in the presence of both Sb(III) and As(III), SbOX exhibited a preference for oxidizing Sb(III). Only after the near complete oxidation of Sb(III) did SbOX initiate rapid oxidation of As(III). In contrast, under anaerobic conditions and in the presence of both Sb(III) and As(III), Sb(III) oxidation notably inhibited the As(III) oxidation pathway in SbOX, while As(III) exhibited minimal effects on the Sb(III) oxidation. These findings suggest that SOPs can oxidize As(III) under both aerobic and anaerobic conditions, exhibiting a strong preference for Sb(III) over As(III) oxidation in the presence of both. This study unveils a novel mechanism of interaction within the Sb and As biogeochemical cycles.
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Antimônio , Oxirredutases , Oxirredutases/metabolismo , Anaerobiose , Antimônio/metabolismo , Oxirredução , Bactérias/metabolismoRESUMO
Fundamento: el síndrome de ovario poliquístico implica oligomenorrea y/o anovulación por exceso de testosterona o LH, además de trastornos metabólicos que pueden resultar en una disminución de los niveles de vitaminas y minerales importantes, incluidos los niveles de zinc y magnesio. Objetivo del estudio: mostrar si el tratamiento con metformina para mujeres de ovario poliquístico puede cambiar los niveles de zinc y magnesio en esas mujeres. Materiales y métodos: este estudio involucra a 23 mujeres de ovario poliquístico diagnosticadas temprano que no toman metformina y 16 mujeres ováricas poliquísticas que toman metformina 850 mg dos veces al día durante al menos tres meses. FSH, LH, testosterona, estradiol, prolactina, SHBG, insulina en ayunas, glucosa en ayunas, magnesio y zinc se miden en el segundo día del ciclo. Resultados: los pacientes sin metformina mostraron aumentos significativos en la relación LH, FSH y testosterona libre en valores de p de 0,03, 0,037 y 0,009 respectivamente. El zinc mostró una correlación directa con el estradiol en pacientes que no recibieron metformina y una correlación indirecta con el índice de masa corporal en pacientes en tratamiento con metformina. Conclusión: el zinc es un elemento importante para la fertilidad femenina, ya que puede mejorar el nivel de estradiol puede deberse a su actividad antioxidante que disminuye la reacción inflamatoria en la región pélvica y mejora la función del ovario. El aumento en el nivel de zinc tiene un efecto inverso en el índice de masa corporal. Sin embargo, el tratamiento con metformina en este estudio no mostró ningún efecto sobre el nivel de magnesio y zinc en mujeres ováricas poliquísticas.
Background: polycystic ovary syndrome involves oligomenorrhea and/ or anovulation due to excess testosterone or LH, in addition to metabolic disorders that may result in decreased levels of important vitamins and minerals, including Zinc and Magnesium levels. Aim of the study: To show if metformin treatment for polycystic ovarian women can change zinc and magnesium levels in those women. Subjects and methods: this study involves 23 early-diagnosed polycystic ovarian women not on metformin and 16 polycystic ovarian women on metformin 850 mg twice daily for at least three months. FSH, LH, testosterone, estradiol, prolactin, SHBG, fasting insulin, fasting glucose, magnesium and zinc are measured on the second day of the cycle. Results: the patients without metformin showed significant increases in LH, LH: SH ratio, and free testosterone at P-values of 0.03, 0.037 and 0.009 respectively. Zinc showed a direct correlation with estradiol in patients not on metformin and an indirect correlation with body mass index in patients on metformin treatment. Conclusion: Zinc is an important element for female fertility as it may enhance estradiol level may be due to its antioxidant activity which decreases the inflammatory reaction in the pelvic region and enhance ovary function. The increase in zinc level has an inverse effect on body mass index. However, metformin treatment in this study showed no effect on the level of magnesium and zinc in polycystic ovarian women.
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Background: The sleep onset process is an ill-defined complex process of transition from wakefulness to sleep, characterized by progressive modifications at the subjective, behavioural, cognitive, and physiological levels. To this date, there is no international consensus which could aid a principled characterisation of this process for clinical research purposes. The current review aims to systemise the current knowledge about the underlying mechanisms of the natural heterogeneity of this process. Methods: In this systematic review, studies investigating the process of the sleep onset from 1970 to 2022 were identified using electronic database searches of PsychINFO, MEDLINE, and Embase. Results: A total of 139 studies were included; 110 studies in healthy participants and 29 studies in participants with sleep disorders. Overall, there is a limited consensus across a body of research about what distinct biomarkers of the sleep onset constitute. Only sparse data exists on the physiology, neurophysiology and behavioural mechanisms of the sleep onset, with majority of studies concentrating on the non-rapid eye movement stage 2 (NREM 2) as a potentially better defined and a more reliable time point that separates sleep from the wake, on the sleep wake continuum. Conclusions: The neurophysiologic landscape of sleep onset bears a complex pattern associated with a multitude of behavioural and physiological markers and remains poorly understood. The methodological variation and a heterogenous definition of the wake-sleep transition in various studies to date is understandable, given that sleep onset is a process that has fluctuating and ill-defined boundaries. Nonetheless, the principled characterisation of the sleep onset process is needed which will allow for a greater conceptualisation of the mechanisms underlying this process, further influencing the efficacy of current treatments for sleep disorders.
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Introduction: The present paper proposes a tool to follow up the compliance of staff and students with biosecurity rules, as enforced in a veterinary faculty, i.e., animal clinics, teaching laboratories, dissection rooms, and educational pig herd and farm. Methods: Starting from a generic list of items gathered into several categories (personal dress and equipment, animal-related items, infrastructures, waste management, management of material/equipment and behavior), a checklist was created for each sector/activity mentioned above, based on the rules and procedures compiled in the Faculty biosecurity standard operating procedures. Checklists were created as Excel™ files. For each sector, several sheets were elaborated, i.e., one per specific activity: for example, the following sheets were created for the equine clinic: class 1-2 hospitalization (class 1 = non-infectious conditions; class 2 = infectious disease with a low or non-existent risk of transmission), class 3 hospitalization (class 3 = infectious disease with a moderate risk of transmission; these patients are suspected of having an infectious disease and being contagious for other patients and/or for humans) and consultation. Results: Class 4 area, which corresponds to the isolation unit and aims at housing patients suffering from infectious diseases with a significant risk of transmission (including notifiable conditions), was not audited at that period, as it was undergoing renovation works. The audit relied on observations performed by a unique observer to ensure standardization. Observed items were presented as yes/no and multiple-choice questions. A scale from 0 to 3 or 4 (depending on the item) allowed scoring each item, i.e., 0 corresponding to 100% compliance with the procedure and the highest score to the worst situation. A median and average global score was also estimated by category and by activity. Discussion: The methodology described in the present paper allows estimating the compliance with biosecurity standard operating procedures in a specific sector and/or for a given activity. The identification of criteria needing improvement is a key point: it helps prioritizing actions to be implemented and awareness raising among people concerned. Regular internal auditing is an essential part of a biosecurity plan, the frequency being conditioned by the risk linked to a specific activity or area (i.e., more frequent audits in risky situations).
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Tandem mass spectrometry is an important analytical tool for clinical laboratories, but tests developed and validated in-house (laboratory developed tests, or LDTs) require special consideration. In late 2022, the forecast for United States (U.S.) federal regulation of LDTs changed unexpectedly when the VALID Act was not passed by the U.S. Congress. This Act would have modified the Food and Drug Administration's (FDA's) role to increase regulatory oversight for LDT providers. In this revised context, we review optimization of quantitative mass spectrometry LDT validation and suggest avenues other than an additional FDA mandate to achieve uniform best practice. Common challenges, logistical barriers, and recommendations for easing the burden of best-quality quantitative mass spectrometry LDT method validation are discussed.
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Many life-threatening diseases remain obscure in their early disease stages. Symptoms appear only at the advanced stage when the survival rate is poor. A non-invasive diagnostic tool may be able to identify disease even at the asymptotic stage and save lives. Volatile metabolites-based diagnostics hold a lot of promise to fulfil this demand. Many experimental techniques are being developed to establish a reliable non-invasive diagnostic tool; however, none of them are yet able to fulfil clinicians' demands. Infrared spectroscopy-based gaseous biofluid analysis demonstrated promising results to fulfil clinicians' expectations. The recent development of the standard operating procedure (SOP), sample measurement, and data analysis techniques for infrared spectroscopy are summarized in this review article. It has also outlined the applicability of infrared spectroscopy to identify the specific biomarkers for diseases such as diabetes, acute gastritis caused by bacterial infection, cerebral palsy, and prostate cancer.
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Gastrite , Masculino , Humanos , Espectrofotometria Infravermelho , Biomarcadores/análise , GasesRESUMO
The rapid growth in the technological advancements of the smartphone industry has classified contemporary smartphones as a low-cost and high quality indoor positioning tools requiring no additional infrastructure or equipment. In recent years, the fine time measurement (FTM) protocol, achieved through the Wi-Fi round trip time (RTT) observable, available in the most recent models, has gained the interest of many research teams worldwide, especially those concerned with indoor localization problems. However, as the Wi-Fi RTT technology is still new, there is a limited number of studies addressing its potential and limitations relative to the positioning problem. This paper presents an investigation and performance evaluation of Wi-Fi RTT capability with a focus on range quality assessment. A set of experimental tests was carried out, considering 1D and 2D space, operating different smartphone devices at various operational settings and observation conditions. Furthermore, in order to address device-dependent and other type of biases in the raw ranges, alternative correction models were developed and tested. The obtained results indicate that Wi-Fi RTT is a promising technology capable of achieving a meter-level accuracy for ranges both in line-of-sight (LOS) and non-line-of-sight (NLOS) conditions, subject to suitable corrections identification and adaptation. From 1D ranging tests, an average mean absolute error (MAE) of 0.85 m and 1.24 m is achieved, for LOS and NLOS conditions, respectively, for 80% of the validation sample data. In 2D-space ranging tests, an average root mean square error (RMSE) of 1.1m is accomplished across the different devices. Furthermore, the analysis has shown that the selection of the bandwidth and the initiator-responder pair are crucial for the correction model selection, whilst knowledge of the type of operating environment (LOS and/or NLOS) can further contribute to Wi-Fi RTT range performance enhancement.
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OBJECTIVES: to investigate the actual selling prices of over-the-counter or self-medication (OTC) and non-prescription (SOP) packages of band C medicines, which are freely set by individual pharmacies, para-pharmacies, and corners of the large-scale retail trade. Specifically, the prices charged for paracetamol 500 mg 20 tablets (20 CPR) and 30 tablets (30 CPR) in the online sale, carried out by different retail outlets authorized by the Italian Ministry of Health, were surveyed. DESIGN: cross-sectional observational descriptive study. The availability for online purchase of one or more packages of paracetamol 500 mg 20 CPR and 30 CPR was checked for each outlet considered; for sites with at least one package available for sale, the lowest real price of each of the two packages (20 and 30 CPR) was recorded, differentiating among: 1. type of outlet (pharmacy or retail outlet); 2. originator (branded) or generic (unbranded) drug; 3. city of residence of the outlet (provincial capital city or not). SETTING AND PARTICIPANTS: the sample considered consists of 475 online retail sites (pharmacies, para-pharmacies, and large-scale retail stores) based in the 10 major Italian provincial capitals, including sites in the relevant provincial cities. MAIN OUTCOME MEASURES: the average real price, calculated as the average of all real prices recorded by packaging type; the minimum real price, i.e., or the lowest real price recorded by packaging type; the average discount, calculated as the difference between the average real price and the average value of the maximum recommended prices (set by the marketing authorization holder, AIC) for branded and unbranded packaging; the maximum discount, calculated as the difference between the minimum real price and the average value of the maximum recommended prices (set by the marketing authorization holder) for branded and unbranded packaging. RESULTS: a wide availability of paracetamol packages produced by multiple AIC holders (both branded and unbranded) was found in the country. The presence of several manufacturers of paracetamol 500 mg induces high price competition, as evident from the discounts given. However, discounts are very high on non-branded packs and lower on branded packs. However, analysis of consumption at the national level shows that price competitiveness does not reflect true market share competitiveness, as consumption is mainly concentrated on branded packs that have the highest prices. CONCLUSIONS: wide and homogeneous distribution of unbranded products from different holders is available throughout the country. These products have significantly lower prices than branded packages, and they also have heavy discounts applied (up to 70%, with minimum price per tablet going as low as 0.05 euros). However, contrary to what these premises might lead one to think, consumption is concentrated on the branded packages having the highest prices. For proper information to citizens and trade associations, it is important for the media to bring awareness of the real savings opportunities available nationwide for products of frequent and widespread use, such as the case of paracetamol 500 mg.