Use of Biomaterials in 3D Printing as a Solution to Microbial Infections in Arthroplasty and Osseous Reconstruction.

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.

Role of Cannabinoids in Oral Cancer.

Cannabinoids have incited scientific interest in different conditions, including malignancy, due to increased exposure to cannabis. Furthermore, cannabinoids are increasingly used to alleviate cancer-related symptoms. This review paper aims to clarify the recent findings on the relationship between cannabinoids and oral cancer, focusing on the molecular mechanisms that could link cannabinoids with oral cancer pathogenesis. In addition, we provide an overview of the current and future perspectives on the management of oral cancer patients using cannabinoid compounds. Epidemiological data on cannabis use and oral cancer development are conflicting. However, in vitro studies assessing the effects of cannabinoids on oral cancer cells have unveiled promising anti-cancer features, including apoptosis and inhibition of cell proliferation. Downregulation of various signaling pathways with anti-cancer effects has been identified in experimental models of oral cancer cells exposed to cannabinoids. Furthermore, in some countries, several synthetic or phytocannabinoids have been approved as medical adjuvants for the management of cancer patients undergoing chemoradiotherapy. Cannabinoids may improve overall well-being by relieving anxiety, depression, pain, and nausea. In conclusion, the link between cannabinoid compounds and oral cancer is complex, and further research is necessary to elucidate the potential risks or their protective impact on oral cancer.

Kaempferol: A Review of Current Evidence of Its Antiviral Potential.

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.

Antimicrobial Properties of Capsaicin: Available Data and Future Research Perspectives.

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.

Comparative Analysis of Hematological and Immunological Parameters in Patients with Primary Sjögren's Syndrome and Peripheral Neuropathy.

BACKGROUND: Primary Sjögren syndrome (pSS) is a multisystem disorder of autoimmune etiology, frequently involving peripheral nerves. Early detection of peripheral neuropathy (PN) manifestations might improve prognosis and disease control. The purpose of the study was to evaluate the predictive potential of hematological and immunological parameters associated with PN development in pSS patients. METHODS: This single-center retrospective study included patients with pSS who were divided into two groups, according to the occurrence of neurological manifestations throughout the follow-up period. RESULTS: From the total of 121 pSS patients included in the study, 31 (25.61%) developed neurological manifestations (PN+ group) during the follow-up period. At the moment of pSS diagnosis, 80.64% of PN+ patients exhibited increased disease activity, with ESSDAI scores above 14 (p = 0.001), and significantly higher values for VASp score (p = 0.001), with a mean value of 4.90 ± 2.45, compared to 1.27 ± 1.32 in the PN- group. The hematological assessment at the moment of pSS diagnosis revealed that neutrophils and neutrophil-to-lymphocyte ratio (NLR) were significantly higher in the PN+ group (p = 0.001), while lymphocytes, monocytes and monocyte-to-lymphocyte ratio (MLR) were significantly lower (p = 0.025, p = 0.13 and p = 0.003, respectively). Immuno-inflammatory parameters-gammaglobulins, complement fractions C3, C4, total proteins and vitamin D were significantly lower in the PN+ patients' group. In multivariate analysis, the independent predictive character for PN development in pSS patients was confirmed for NLR (95% CI 0.033 to 0.263, p = 0.012), MLR (95% CI -1.289 to -0.194, p = 0.008), gammaglobulins (95% CI -0.426 to -0.088, p < 0.003), complement fraction C4 (95% CI -0.018 to -0.001, p < 0.030) and vitamin D (95% CI -0.017 to -0.003, p < 0.009). CONCLUSIONS: Readily available and frequently used hematological and immunological markers, such as NLR, MLR, gammaglobulins, C4 and vitamin D could be helpful in predicting the neurological involvement in pSS patients. These biological parameters might become useful tools for clinicians to monitor disease progression and identify potentially severe extraglandular manifestations in pSS patients.

Current Approach and Future Directions in the Diagnosis and Prognosis of Keratinocyte Carcinomas.

Keratinocyte carcinomas (KCs) are malignancies developed from keratinocytes or their precursors [...].

The Spectrum of Extraglandular Manifestations in Primary Sjögren's Syndrome.

Extraglandular manifestations (EGMs) in primary Sjogren's syndrome (pSS) represent the clinical expression of the systemic involvement in this disease. EGMs are characterized by a wide heterogeneity; virtually any organ or system can be affected, with various degrees of dysfunction. The existing gaps of knowledge in this complex domain of extraglandular extension in pSS need to be overcome in order to increase the diagnostic accuracy of EGMs in pSS. The timely identification of EGMs, as early as from subclinical stages, can be facilitated using highly specific biomarkers, thus preventing decompensated disease and severe complications. To date, there is no general consensus on the diagnostic criteria for the wide range of extraglandular involvement in pSS, which associates important underdiagnosing of EGMs, subsequent undertreatment and progression to severe organ dysfunction in these patients. This review article presents the most recent basic and clinical science research conducted to investigate pathogenic mechanisms leading to EGMs in pSS patients. In addition, it presents the current diagnostic and treatment recommendations and the trends for future therapeutic strategies based on personalized treatment, as well as the latest research in the field of diagnostic and prognostic biomarkers for extraglandular involvement in pSS.

Skin Cancer Pathobiology at a Glance: A Focus on Imaging Techniques and Their Potential for Improved Diagnosis and Surveillance in Clinical Cohorts.

Early diagnosis is essential for completely eradicating skin cancer and maximizing patients' clinical benefits. Emerging optical imaging modalities such as reflectance confocal microscopy (RCM), optical coherence tomography (OCT), magnetic resonance imaging (MRI), near-infrared (NIR) bioimaging, positron emission tomography (PET), and their combinations provide non-invasive imaging data that may help in the early detection of cutaneous tumors and surgical planning. Hence, they seem appropriate for observing dynamic processes such as blood flow, immune cell activation, and tumor energy metabolism, which may be relevant for disease evolution. This review discusses the latest technological and methodological advances in imaging techniques that may be applied for skin cancer detection and monitoring. In the first instance, we will describe the principle and prospective clinical applications of the most commonly used imaging techniques, highlighting the challenges and opportunities of their implementation in the clinical setting. We will also highlight how imaging techniques may complement the molecular and histological approaches in sharpening the non-invasive skin characterization, laying the ground for more personalized approaches in skin cancer patients.

Biomaterials Adapted to Vat Photopolymerization in 3D Printing: Characteristics and Medical Applications.

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.

Kaempferol: Antimicrobial Properties, Sources, Clinical, and Traditional Applications.

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.

Recent Advances in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC), the most frequent of head and neck cancers, has been a topic of great interest to the scientific community [...].

Reply to Çinar et al. Comment on "Zamfir et al. Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases. Medicina 2022, 58, 874".

We would like to thank Çinar et al. for their appreciation and insightful discussions presented in their comment [...].

The Predictive Role of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocytes-to-Lymphocyte Ratio (MLR) and Gammaglobulins for the Development of Cutaneous Vasculitis Lesions in Primary Sjögren's Syndrome.

Background: In primary Sjögren's Syndrome (pSS), cutaneous vasculitis lesions (CVL) are extraglandular manifestations with an important clinical and prognostic impact and their early detection might contribute to the improvement of disease control and even patients' survival. The aim of this study was to evaluate the predictive potential of hematological elements in the development of CVL in pSS patients. Methods: In this single center, retrospective study, a total of 245 participants were included (124 pSS patients and 121 healthy controls). Complete blood count, inflammatory and immunological parameters were determined at the initial visit. pSS patients underwent a periodical follow-up program, when disease progression and response to therapy was monitored, including the emergence of CVL. Results: In pSS, leucocytes, lymphocyte, neutrophil, monocyte, erythrocyte and platelet counts are significantly decreased compared to healthy subjects (p < 0.001), whereas cellular ratios: NLR, PLR, MLR, and immunological and inflammatory parameters are significantly increased (p < 0.001). A total of 34 patients with pSS (27.41%) developed CVL during the follow-up period. The occurrence of CVL was positively correlated with neutrophil and platelet counts (p < 0.001), while for lymphocytes the correlation was negative (p < 0.001). Cellular ratios: NLR, PLR and MLR, and gammaglobulins also revealed significant positive correlations with the emergence of CVL in pSS (p < 0.001). The multivariate analysis confirmed the independent predictive character for CVL emergence in pSS for NLR (CI95% 0.053−0.2, p < 0.002), PLR (CI95% 0.001−0.003, p < 0.003), MLR (CI95% 0.086−0.935, p < 0.019), and gammaglobulins (CI95% 0.423−0.688, p < 0.001). Conclusions: Standard hematological parameters, widely used in the assessment of pSS patients, such as NLR, PLR, MLR and gammaglobulins could become valid elements that might be used for the early detection of patients at risk for the development of CVL.

The Assessment of Serum Cytokines in Oral Squamous Cell Carcinoma Patients: An Observational Prospective Controlled Study.

Background: The oral squamous cell carcinoma (OSCC) tumor microenvironment (TME) is a complex interweb of cells and mediators balancing carcinogenesis, inflammation, and the immune response. However, cytokines are not only secreted within the TME but also released by a variety of other cells that do not comprise the TME; therefore, a thorough assessment of humoral changes in OSCC should include the measurement of serum cytokines. Methods: We assessed the role of various serum cytokines in the evolution of OSCC, before and after treatment, versus a control group. We measured the serum concentrations of MIP-1α, IL-1ß, IL-4, IL-6, IL-8, IL-10, and TNF-α. Results: Significantly higher values (p < 0.01) were noted for IL-1ß, IL-6, IL-8, IL-10, and TNF-α in the OSCC group before treatment (n = 13) compared with the control group (n = 14), and the increased concentrations persisted after treatment (n = 11). Furthermore, the variations in the values of MIP-1α, IL-1ß, IL-10, and TNF-α are correlated both before and after treatment (p < 0.01). In the pretherapeutic group, IL-6 and IL-8 concentrations also correlate with IL-1ß and IL-10 serum levels (p < 0.01), while in the posttherapeutic group, IL-4 varies with MIP-1α and TNF-α (p < 0.01). Conclusion: In OSCC patients, serum cytokine levels are significantly higher compared with control, but they are not significantly altered by treatment, therefore implying that they are also influenced by systemic factors. The interactions between all involved cytokines and the various pathways they regulate warrant further studies to clarify their definitive roles.

PLGA Nanoparticles Uptake in Stem Cells from Human Exfoliated Deciduous Teeth and Oral Keratinocyte Stem Cells.

Polymeric nanoparticles have been introduced as a delivery vehicle for active compounds in a broad range of medical applications due to their biocompatibility, stability, controlled release of active compounds, and reduced toxicity. The oral route is the most used approach for delivery of biologics to the body. The homeostasis and function of oral cavity tissues are dependent on the activity of stem cells. The present work focuses, for the first time, on the interaction between two types of polymeric nanoparticles, poly (lactic-co-glycolic acid) or PLGA and PLGA/chitosan, and two stem cell populations, oral keratinocyte stem cells (OKSCs) and stem cells from human exfoliated deciduous teeth (SHEDs). The main results show that statistical significance was observed in OKSCs uptake when compared with normal keratinocytes and transit amplifying cells after 24 h of incubation with 5 and 10 µg/mL PLGA/chitosan. The CD117+ SHED subpopulation incorporated more PLGA/chitosan nanoparticles than nonseparated SHED. The uptake for PLGA/chitosan particles was better than for PLGA particles with longer incubation times, yielding better results in both cell types. The present results demonstrate that nanoparticle uptake depends on stem cell type, incubation time, particle concentration, and surface properties.

Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases.

BACKGROUND: During the last two years, the COVID-19 pandemic led to millions of disease-related deaths worldwide. The efforts of the scientific community facing this global challenge resulted in outstanding achievements. Thus, within one year, new mRNA-based vaccines against SARS-CoV-2 viral infection were released, providing highly efficient protection and showing a very good safety profile in the general population. However, clinical data collection after vaccination is a continuous process for the long-term safety of any new medical product. The aim of our paper is to present two cases of hematological malignancies: diffuse large B-cell non-Hodgkin lymphoma and T/NK-cell lymphoma, diagnosed shortly after the administration of the mRNA COVID-19 vaccine. METHODS AND RESULTS: Case 1: A female patient was admitted with a suspicious cervical mass that emerged within one week after the administration of second dose of the BNT162b2 COVID-19 vaccine. Surgical removal followed by pathology assessment of the specimen confirmed the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Case 2: A male patient was admitted with multiple ulcerative oral lesions arising on the third day after the initial dose of the BNT162b2 COVID-19 vaccine. These lesions had a progressive character and during the following months were complicated with repetitive episodes of heavy oral bleeding, requiring blood transfusions. The incisional biopsy of the lesions and pathological assessment of the specimens confirmed the diagnosis of T/NK-cell lymphoma. CONCLUSIONS: The safety profile of the mRNA-based vaccines is an undeniable fact. In most cases, suspicions of potentially aggressive side effects were ruled out, proving to be transient post-vaccine reactions. Clinicians should remain alert to report any potentially aggressive manifestations emerging in the context of mRNA COVID-19 vaccination, such as these cases of hematological malignancies, in order to promote additional investigations on the particular mechanisms of action of COVID-19 vaccines and to provide the best medical care to the patients.

Assessment of Serum Urea, Creatinine and Uric Acid in Oral Cancer.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a common malignancy worldwide, leading to significant disease-associated social and financial burdens. The investigation of underlying mechanisms involved in carcinogenesis and tumor progression in OSCC might provide new therapeutic perspectives with an impact on disease control and patient survival. Our study aims to investigate the interrelation between metabolic processes, expressed through final catabolism products and clinicopathological characteristics in OSCC. MATERIALS AND METHODS: This is a single cancer comparative retrospective study investigating metabolic byproducts, namely serum urea, creatinine and uric acid, detected at the moment of diagnosis in patients with OSCC, in comparison to healthy controls. Clinical and paraclinical data regarding exposure to risk factors, disease staging and pathological characteristics were collected for all patients. Subjects with co-existing systemic or metabolic diseases, or with a history of malignancy, were excluded from the study. Subsequently, the metabolic byproducts revealing significant changes in OSCC patients were considered for a correlation analysis with the disease clinico-pathological characteristics. RESULTS: Blood levels for urea, creatinine and uric acid were determined in a total of 225 subjects: 145 patients diagnosed with OSCC and 80 healthy control subjects admitted to our hospital between 2016 and 2021. The comparative analysis between groups revealed that the serum urea level was significantly lower in OSCC patients (p = 0.0344). Serum creatinine and uric acid did not reveal significant differences between groups. Furthermore, in advanced stages of the disease (stages III and IV), the blood level of urea was significantly lower compared to incipient OSCC (stages I and II) (p = 0.003). We found a negative correlation of serum urea levels with smoking (p = 0.0004) and cervical lymph node metastasis (p = 0.0070), and a positive correlation with aging (p = 0.0000). We found no significant correlation of serum urea with primary tumor size (p = 0.5061) and patient survival (p = 0.2932). CONCLUSIONS: Decreased serum urea levels are detected in patients with advanced OSCC, in correlation with lymph node metastasis. The invasive features of tumor cells in OSCC might be promoted in association with dysregulation of protein catabolism processes, facilitating aggressive behavior in OSCC.

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis.

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism's response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.

A combination of two regional flaps for the complex reconstruction after head and neck cancer surgery as an alternative approach during the COVID-19 pandemic: A case report.

Since the COVID-19 pandemic outbreak, the medical systems were challenged by continuously increasing numbers of infections and faced critical issues when trying to find solutions for patients suffering from other diseases, including patients with head and neck cancers. Complex surgeries were delayed due to an acute deficit of specialized intensive care medical staff and equipment, which were redirected towards COVID-19 hospitalized cases, with irreversible consequences for the patients. In the present study, the case of locally advanced head and neck cancer was presented, which was treated radically during the heaviest wave of the COVID-19 pandemic in Romania using an alternative approach for immediate defect reconstruction. The case of locally advanced buccal carcinoma (staged T4aN0Mx) was reported, where radical tumor excision was followed by immediate reconstruction using a combination of two regional flaps, temporal and submental, in order to provide timely and optimal medical care. In the difficult context of the COVID-19 pandemic, the standard reconstructive technique, which is the free vascularized tissue transfer, could not be performed for this patient, due to the acute deficit of anesthetists and associated medical staff, as well as the lack of free beds in intensive care units. Combinations of local and regional flaps, such as temporal muscle flap and submental flap, are simple and accessible surgical techniques that require reduced surgical time, minimal equipment, and basic surgical training, advantages that become crucial in historically challenging times, such as a global pandemic. Individual cases, like elderly patients or patients with severe comorbidities, should be considered for these types of reconstructive techniques: simple solutions, single or in combination, which may be an improved therapeutic option for these patients.

Availability, Toxicology and Medical Significance of Antimony.

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.