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Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin's anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.
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Artificial Intelligence (AI) is redefining electrocardiogram (ECG) analysis in pre-participation examination (PPE) of athletes, enhancing the detection and monitoring of cardiovascular health. Cardiovascular concerns, including sudden cardiac death, pose significant risks during sports activities. Traditional ECG, essential yet limited, often fails to distinguish between benign cardiac adaptations and serious conditions. This narrative review investigates the application of machine learning (ML) and deep learning (DL) in ECG interpretation, aiming to improve the detection of arrhythmias, channelopathies, and hypertrophic cardiomyopathies. A literature review over the past decade, sourcing from PubMed and Google Scholar, highlights the growing adoption of AI in sports medicine for its precision and predictive capabilities. AI algorithms excel at identifying complex cardiac patterns, potentially overlooked by traditional methods, and are increasingly integrated into wearable technologies for continuous monitoring. Overall, by offering a comprehensive overview of current innovations and outlining future advancements, this review supports sports medicine professionals in merging traditional screening methods with state-of-the-art AI technologies. This approach aims to enhance diagnostic accuracy and efficiency in athlete care, promoting early detection and more effective monitoring through AI-enhanced ECG analysis within athlete PPEs.
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Pulmonary oncological pathologies are an important public health problem and the association with other pulmonary lesions may pose difficulties in diagnosis and staging or require different treatment options. To address this complexity, we conducted a retrospective observational study at the Marius Nasta Institute of Pneumophthisiology, Bucharest, Romania. Our study focused on patients admitted in 2019 with non-small-cell lung carcinoma and associated pulmonary lesions identified through surgical resection specimens. Among the 314 included patients, multiple pulmonary nodules were observed on macroscopic examination, with 12% (N = 37) exhibiting nonmalignant etiologies upon microscopic examination. These findings underscore the challenge of preoperative staging. Patients with coexisting nonmalignant lesions were similar in age, smoking habits, and professional or environmental exposure by comparison with those who presented only malignant lesions. The presentation of coexisting malignant and nonmalignant lesions may pose difficulties in diagnosing and staging pulmonary cancer.
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Background and Objectives: The mainstay treatment of non-small-cell lung carcinoma is still surgery, but its impact on survival beyond nine years has never been reported/analysed in Romania. Therefore, we studied the clinical characteristics and the short- and long-term survival of a population of 1369 patients diagnosed and treated in a single institution, with the variables included in the database being collected retrospectively. Materials and Methods: In this paper, we aimed to study a number of factors that might influence prognosis and survival in non-small bronchopulmonary carcinoma. Consequently, we analysed a series of parameters such as the age of patients, their sex, the histopathological type, the tumour stage, the presence of bronchial invasion, and the completeness of surgical resection. Results: All patients underwent major lung resection for curative purposes (pneumonectomy, lobectomy, or bilobectomy) between January 2015 and January 2023. The vital status of patients included in the study was obtained by checking the DGEP (General Directorate for Persons Record) database and verifying the reporting of "non-deceased" by the hospital administrative database, as well as by telephone interviews (with patients or their relatives). On univariate analysis, predictors of worse survival were the following: male sex (the hazard of death was 1.54 times higher in men); pT (compared to pT1 tumours, pT2 tumours have a 1.60 times higher hazard of death, pT3 tumours have a 2.16 times higher hazard, and pT4 tumours have a 2.97 times higher hazard); maximum tumour size (a 10 mm increase in tumour size is associated with a 10% increase in the hazard of death); the degree of differentiation (compared to patients with G1 tumours, those with G3 tumours have a 2.16 times higher hazard of death); resectability (compared to R0, R1 B+ has a 1.84 times higher hazard of death, R1 V+ has a 1.82 times higher hazard of death, and R1 B+&V+ has a 2.40 times higher hazard of death). Conclusions: As a result, long-term survival can be achieved after complete surgery for NSCLC, and factors that classically predict overall survival suggest that both the initial tumour aggressiveness and host characteristics act beyond the period usually considered in oncology.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Masculino , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Prognóstico , Pneumonectomia , Estadiamento de NeoplasiasRESUMO
The incidence of microbial infections in orthopedic prosthetic surgeries is a perennial problem that increases morbidity and mortality, representing one of the major complications of such medical interventions. The emergence of novel technologies, especially 3D printing, represents a promising avenue of development for reducing the risk of such eventualities. There are already a host of biomaterials, suitable for 3D printing, that are being tested for antimicrobial properties when they are coated with bioactive compounds, such as antibiotics, or combined with hydrogels with antimicrobial and antioxidant properties, such as chitosan and metal nanoparticles, among others. The materials discussed in the context of this paper comprise beta-tricalcium phosphate (ß-TCP), biphasic calcium phosphate (BCP), hydroxyapatite, lithium disilicate glass, polyetheretherketone (PEEK), poly(propylene fumarate) (PPF), poly(trimethylene carbonate) (PTMC), and zirconia. While the recent research results are promising, further development is required to address the increasing antibiotic resistance exhibited by several common pathogens, the potential for fungal infections, and the potential toxicity of some metal nanoparticles. Other solutions, like the incorporation of phytochemicals, should also be explored. Incorporating artificial intelligence (AI) in the development of certain orthopedic implants and the potential use of AI against bacterial infections might represent viable solutions to these problems. Finally, there are some legal considerations associated with the use of biomaterials and the widespread use of 3D printing, which must be taken into account.
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Kaempferol and its derivatives are flavonoids found in various plants, and a considerable number of these have been used in various medical applications worldwide. Kaempferol and its compounds have well-known antioxidant, anti-inflammatory and antimicrobial properties among other health benefits. However, the antiviral properties of kaempferol are notable, and there is a significant number of experimental studies on this topic. Kaempferol compounds were effective against DNA viruses such as hepatitis B virus, viruses of the alphaherpesvirinae family, African swine fever virus, and pseudorabies virus; they were also effective against RNA viruses, namely feline SARS coronavirus, dengue fever virus, Japanese encephalitis virus, influenza virus, enterovirus 71, poliovirus, respiratory syncytial virus, human immunodeficiency virus, calicivirus, and chikungunya virus. On the other hand, no effectiveness against murine norovirus and hepatitis A virus could be determined. The antiviral action mechanisms of kaempferol compounds are various, such as the inhibition of viral polymerases and of viral attachment and entry into host cells. Future research should be focused on further elucidating the antiviral properties of kaempferol compounds from different plants and assessing their potential use to complement the action of antiviral drugs.
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Vírus da Febre Suína Africana , Enterovirus , Vírus de RNA , Suínos , Animais , Gatos , Humanos , Camundongos , Quempferóis/farmacologia , Antivirais/farmacologiaRESUMO
Capsaicin is a phytochemical derived from plants of the genus Capsicum and subject of intensive phytochemical research due to its numerous physiological and therapeutical effects, including its important antimicrobial properties. Depending on the concentration and the strain of the bacterium, capsaicin can exert either bacteriostatic or even bactericidal effects against a wide range of both Gram-positive and Gram-negative bacteria, while in certain cases it can reduce their pathogenicity by a variety of mechanisms such as mitigating the release of toxins or inhibiting biofilm formation. Likewise, capsaicin has been shown to be effective against fungal pathogens, particularly Candida spp., where it once again interferes with biofilm formation. The parasites Toxoplasma gondi and Trypanosoma cruzi have been found to be susceptible to the action of this compound too while there are also viruses whose invasiveness is significantly dampened by it. Among the most encouraging findings are the prospects for future development, especially using new formulations and drug delivery mechanisms. Finally, the influence of capsaicin in somatostatin and substance P secretion and action, offers an interesting array of possibilities given that these physiologically secreted compounds modulate inflammation and immune response to a significant extent.
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Anti-Infecciosos , Capsaicina , Capsaicina/farmacologia , Antibacterianos/farmacologia , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Anti-Infecciosos/farmacologia , Compostos FitoquímicosRESUMO
Gifted children exhibit advanced cognitive abilities, usually beyond their emotional development, which puts them at higher risk of the negative consequences of isolation. This study investigates the effects of distance learning and home confinement on the emotional and social stability, motivation, and attitudes of gifted and non-gifted children in Greece. Our study includes two subsets, from before (September 2017 to March 2020) and after the outbreak of the COVID-19 pandemic (April 2020 to March 2022). The analysis indicated that home confinement and distance learning caused children to create a stronger attachment with their parents, and it increased the involvement of parents in their child's school experience. Non-gifted children displayed high levels of certain attitudes (perfectionism, desire for acceptance, and condescending behavior) and demonstrated elevated motivation. Gifted children in the pre-COVID-19 period had already displayed increased levels of condescending attitude, which is assumed to be the result of already existing expectations from their parents. The pandemic further increased this attitude, as a result of the higher expectations of their parents. Overall, the study highlighted the importance of children to have more than one support system and the need for them to strengthen their self-image.
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Pulmonary hematomas are a rare pathology. Although they are usually reported post-traumatically, there are also spontaneous forms in pulmonary pathologies or during drug therapy. In these spontaneous entities, primitive forms are rarely described, although the contributory local pulmonary pathological terrain or a specific associated medication has not yet been identified. We present the case of a patient who developed a giant pulmonary hematoma that appeared spontaneously during recovery from COVID-19 infection. It appeared in one of the two bullae-like cystic lung lesions developed during secondary COVID-19 infection. The clinical impact was major, with hypotension and anemia being observed, requiring hemodynamic support and the adjustment of drug therapy. The clinical course was favorable, with a quasi-complete resolution of both the hematoma and a second cystic lesion being observable at 8 months by pulmonary remodeling. Spontaneous pulmonary hematomas may constitute a pathological entity associated with a post-COVID-19 remodeling process of the lung and the related anticoagulant treatment, which should be recognized, especially in the actual COVID-19 pandemic or in the widespread use of anticoagulant treatment. Conservative treatment is the method of choice, even in giant lung forms.
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Along with the rapid and extensive advancements in the 3D printing field, a diverse range of uses for 3D printing have appeared in the spectrum of medical applications. Vat photopolymerization (VPP) stands out as one of the most extensively researched methods of 3D printing, with its main advantages being a high printing speed and the ability to produce high-resolution structures. A major challenge in using VPP 3D-printed materials in medicine is the general incompatibility of standard VPP resin mixtures with the requirements of biocompatibility and biofunctionality. Instead of developing completely new materials, an alternate approach to solving this problem involves adapting existing biomaterials. These materials are incompatible with VPP 3D printing in their pure form but can be adapted to the VPP chemistry and general process through the use of innovative mixtures and the addition of specific pre- and post-printing steps. This review's primary objective is to highlight biofunctional and biocompatible materials that have been adapted to VPP. We present and compare the suitability of these adapted materials to different medical applications and propose other biomaterials that could be further adapted to the VPP 3D printing process in order to fulfill patient-specific medical requirements.
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Flavonoids are a category of plant-derived compounds which exhibit a large number of health-related effects. One of the most well-known and studied flavonoids is kaempferol, which can be found in a wide variety of herbs and plant families. Apart from their anticarcinogenic and anti-inflammatory effects, kaempferol and its associated compounds also exhibit antibacterial, antifungal, and antiprotozoal activities. The development of drugs and treatment schemes based on these compounds is becoming increasingly important in the face of emerging resistance of numerous pathogens as well as complex molecular interactions between various drug therapies. In addition, many of the kaempferol-containing plants are used in traditional systems all over the world for centuries to treat numerous conditions. Due to its variety of sources and associated compounds, some molecular mechanisms of kaempferol antimicrobial activity are well known while others are still under analysis. This paper thoroughly documents the vegetal and food sources of kaempferol as well as the most recent and significant studies regarding its antimicrobial applications.
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Anti-Infecciosos , Antiprotozoários , Quempferóis/farmacologia , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Antibacterianos , FlavonoidesRESUMO
BACKGROUND: Crohn's disease and ulcerative hemorrhagic colitis are forms of granulomatous inflammatory intestinal disease, which usually affects the gastrointestinal tract. There are also reported rare localizations at the skin, kidney, joints, liver and eye level. Pulmonary involvement is relatively rare, and it is most commonly reported in suppuration with bronchiectasis. On the other hand, sarcoidosis is, in principle, a thoracic localization of a granulomatosis disease, although bowel, skin and intestinal disorders are described. There is not a clear line to separate Crohn's disease from sarcoidosis with, possibly because they are, in fact, considered to have the same inflammatory granulomatosis disease pathology. The diagnoses of the two entities, sarcoidosis and Crohn's disease, are based on non-pathognomonic, inclusive clinical and paraclinical criteria, without elements of the mutual exclusion of typical locations. CASE REPORT: We present a very rare case of a young male, already diagnosed with small-bowel Crohn's disease. Granulomatous lung disease with major hemoptysis requires emergency surgery. An intraoperative assessment revealed a necrotic hemorrhagic lesion located in the left lower lobe and a lobectomy was performed. The final pathological report showed the presence of non-caseous granulomatous inflammation, with the identification of specific multinucleated giant cells. CONCLUSIONS: The identical diagnostic principles of Crohn's disease and sarcoidosis, Crohn's disease as a predecessor to pulmonary lesions, the clinical picture and the necrotico-hemorrhagic appearance of the unilateral pulmonary lesion, which are similar to aggressive necrotico-hemorrhagic or perforating intestinal forms, are arguments in favor of the diagnosis of pulmonary Crohn's disease and not pulmonary sarcoidosis. At the same time, in general, the two diseases have overlapping elements, suggesting they are, in fact, not the same disease with different facets.
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Background and aims: Our aim is to examine the relationship between the level of education, background, tumor size and lymph node status on the treatment outcome in a group of patients with early and locally advanced breast cancer (BC) by using the restricted mean survival time (RMST), which summarizes treatment effects in terms of event-free time over a fixed period of time. Methods: We evaluated the prognostic values in 143 patients treated for early BC at Elias University Emergency Hospital, Bucharest, Romania and followed up for a maximum of 36 months. The protocol was amended to include the levels of education (gymnasium, high school, or university), the background (urban or rural) and the clinical stage (primary tumor (T) and regional nodes (N)). The methodology consisted in using a Kaplan-Meier analysis and RMST for the entire sample and Cox regression, for the variables with statistical influence. The principal endpoints of the study were overall survival (OS) and progression free survival (PFS). Results: The level of education had impact both on RMST OS (35.30 vs. 26.70) and death HR (hazard ratio) in the group of patients with general school level, compared with those with graduated university. In this study, the urban or rural background did not impact the outcome, probably because in this study we included predominantly patients from urban areas (83%). Although clinical tumor size measurements did not impact the outcome, the clinical staged lymph node influenced both OS (p=0.0500) and PFS (p=0.0006) for the patients with palpable or imaging proof of lymph node involvement of station 2 or 3. Conclusions: RMST provides an intuitive and explicit way to express the effect of those risk factors on OS and PFS in a cohort of early breast cancer patients. Low level of education and high-grade clinical lymph node status negatively influences the outcome of this cohort of BC patients.
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Antimony has been known and used since ancient times, but its applications have increased significantly during the last two centuries. Aside from its few medical applications, it also has industrial applications, acting as a flame retardant and a catalyst. Geologically, native antimony is rare, and it is mostly found in sulfide ores. The main ore minerals of antimony are antimonite and jamesonite. The extensive mining and use of antimony have led to its introduction into the biosphere, where it can be hazardous, depending on its bioavailability and absorption. Detailed studies exist both from active and abandoned mining sites, and from urban settings, which document the environmental impact of antimony pollution and its impact on human physiology. Despite its evident and pronounced toxicity, it has also been used in some drugs, initially tartar emetics and subsequently antimonials. The latter are used to treat tropical diseases and their therapeutic potential for leishmaniasis means that they will not be soon phased out, despite the fact the antimonial resistance is beginning to be documented. The mechanisms by which antimony is introduced into human cells and subsequently excreted are still the subject of research; their elucidation will enable us to better understand antimony toxicity and, hopefully, to improve the nature and delivery method of antimonial drugs.
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Antimônio , Leishmaniose , Antimônio/análise , Antimônio/toxicidade , Humanos , Minerais , MineraçãoRESUMO
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and affects about 8% of cirrhotic patients, with a recurrence rate of over 50%. There are numerous therapies available for the treatment of HCC, depending on cancer staging and condition of the patient. The complexity of the treatment is also justified by the unique pathogenesis of HCC that involves intricate processes such as chronic inflammation, fibrosis, and multiple molecular carcinogenesis events. During the last three decades, multiple in vivo and in vitro experiments have used somatostatin and its analogs (SSAs) to reduce the proliferative and metastatic potential of hepatoma cells by inducing their apoptosis and reducing angiogenesis and the inflammatory component of HCC. Most experiments have proven successful, revealing several different pathways and mechanisms corresponding to the aforementioned functions. Moreover, a correlation between specific effects and expression of somatostatin receptors (SSTRs) was observed in the studied cells. Clinical trials have tested either somatostatin or an analog, alone or in combination with other drugs, to explore the potential effects on HCC patients, in various stages of the disease. While the majority of these clinical trials exhibited minor to moderate success, some other studies were inconclusive or even reported negative outcomes. A complete evaluation of the efficacy of somatostatin and SSAs is still the matter of intense debate, and, if deemed useful, these substances may play a beneficial role in the management of HCC patients.
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Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Somatostatina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Receptores de Somatostatina/metabolismo , Somatostatina/análogos & derivadosRESUMO
This study aimed to investigate the relationship between somatic symptom disorder (SSD) and sleep disorders, following three research questions: (1) How are these disorders correlated? (2) What are the comorbidities reported in these patients? and (3) What are the most effective pharmacological and non-pharmacological treatments for both conditions? PubMed, Scopus, OVID, Medline, and ProQuest databases were searched for relevant articles published between 1957-2020. Search terms included "somatic symptoms disorder", "sleep disorders", "insomnia", "somatoform", "somatization", "therapeutic", "psychotherapy", and alternative, formerly used terms for SSD. Forty papers were finally included in the study. Prevalence of insomnia in SSD patients ranged between 20.4-48%, with this being strongly correlated to somatic symptoms and psychosocial disability. The most relevant comorbidities were generalized anxiety disorder, depression, fatigue, negative mood, substance use, orthorexia, alexithymia, anorexia, weight loss, poor eating habits, and acute stress disorder. Patients receiving antidepressant therapy reported significant improvements in insomnia and somatic symptoms. In terms of non-pharmacological interventions, cognitive-behavioral therapy (CBT) showed improvements in sleep outcomes, while the Specialized Treatment for Severe Bodily Distress Syndromes (STreSS) may represent an additional promising option. Future research could include other medical and psychosocial variables to complete the picture of the relationship between sleep disorders and somatic symptoms.
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BACKGROUND AND AIM: Breast cancer (BC) is the most common malignancy among women worldwide, and one of the leading causes of cancer-related deaths in females. For the breast malignant tumors there are numerous targeted therapies, depending on the receptors expressed. Regulating the process of epithelial-mesenchyme transcription, the steroid nuclear receptors are important in invasion and progression of BC cells. Till now, it is known that androgen receptor (AR) is present in about 60-80% of BC cells but, unfortunately, there is no targeted therapy available yet. METHODS: We revised the recent literature that included the AR mechanism of action in patients diagnosed with breast cancer, the preclinical, retrospective and clinical studies and the aspects related to the prognosis of these patients, depending on the molecular subtype. RESULTS: A total of 12 articles were eligible for this review. AR positivity was assessed using immunohistochemistry. Herein, neither 1 nor 10% cut-points were robustly prognostic. AR was an independent prognostic marker of BC outcome, especially in triple negative BC group. CONCLUSION: AR is a potential targeted pathway which can improve the prognostic of AR positive patients with BC. Further preclinical and clinical studies are necessary to clarify the mechanism of action and to establish the drugs which can be used, either alone or in combination.
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Chronic obstructive pulmonary disease (COPD) and asthma are chronic respiratory diseases with high prevalence and mortality that significantly alter the quality of life in affected patients. While the cellular and molecular mechanisms engaged in the development and evolution of these two conditions are different, COPD and asthma share a wide array of symptoms and clinical signs that may impede differential diagnosis. However, the distinct signaling pathways regulating cough and airway hyperresponsiveness employ the interaction of different cells, molecules, and receptors. Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays a major role in cough and airway inflammation. Consequently, its agonist, capsaicin, is of substantial interest in exploring the cellular effects and regulatory pathways that mediate these respiratory conditions. Increasingly more studies emphasize the use of capsaicin for the inhalation cough challenge, yet the involvement of TRPV1 in cough, bronchoconstriction, and the initiation of inflammation has not been entirely revealed. This review outlines a comparative perspective on the effects of capsaicin and its receptor in the pathophysiology of COPD and asthma, underlying the complex entanglement of molecular signals that bridge the alteration of cellular function with the multitude of clinical effects.
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Recent studies have identified great similarities and interferences between the epithelial layers of the digestive tract, the airways and the cutaneous layer. The relationship between these structures seems to implicate signaling pathways, cellular components and metabolic features, and has led to the definition of a gut-lung-skin barrier. Inflammation seems to involve common features in these tissues; therefore, analyzing the similarities and differences in the modulation of its biomarkers can yield significant data promoting a better understanding of the particularities of specific signaling pathways and cellular effects. Cannabinoids are well known for a wide array of beneficial effects, including anti-inflammatory properties. This paper aims to explore the effects of natural and synthetic cannabinoids, including the components of the endocannabinoid system, in relation to the inflammation of the gut-lung-skin barrier epithelia. Recent advancements in the use of cannabinoids as anti-inflammatory substances in various disorders of the gut, lungs and skin are detailed. Some studies have reported mixed or controversial results, and these have also been addressed in our paper.
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BACKGROUND: We investigated the correlation between the androgen receptor (AR) and immunohistochemistry (IHC) as a prognostic factor in breast cancer (BC). AR is expressed in 60-80% of BC. METHODS: We evaluated the prognostic values of AR expression among 143 patients with BC for 36 months. The protocol was amended to measure androgen, estrogen and progesterone receptor expression by IHC and the percentage of hormone positive nuclei was quantified. We determined and quantified the Her2/neu status using IHC and in situ hybridization. The methodology consisted in using a Kaplan-Meier analysis and restricted mean survival time up to 36 months. The principal endpoints of the study were overall survival (OS) and progression free survival (PFS). RESULTS: 57% of patients (n = 82) from our group had AR+ (≥ 1%). Patients with AR+ had better OS, 35.50 vs. 33.40 months, with p = 0.027. Moreover, PFS was prolonged for patients AR+, 32.60 vs. 30.50 months, with p = 0.38. Triple negative breast cancer (TNBC) patients had lower OS and no difference was observed for PFS. CONCLUSIONS: Both OS and PFS were favorably influenced by the presence of AR. TNBC had worse outcomes compared with patients with hormonal or/and Her 2/neu positive disease in terms of OS.