Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies.

Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.

Inhibition or Reversal of the Epithelial-Mesenchymal Transition in Gastric Cancer: Pharmacological Approaches.

Epithelial-mesenchymal transition (EMT) constitutes one of the hallmarks of carcinogenesis consisting in the re-differentiation of the epithelial cells into mesenchymal ones changing the cellular phenotype into a malignant one. EMT has been shown to play a role in the malignant transformation and while occurring in the tumor microenvironment, it significantly affects the aggressiveness of gastric cancer, among others. Importantly, after EMT occurs, gastric cancer patients are more susceptible to the induction of resistance to various therapeutic agents, worsening the clinical outcome of patients. Therefore, there is an urgent need to search for the newest pharmacological agents targeting EMT to prevent further progression of gastric carcinogenesis and potential metastases. Therapies targeted at EMT might be combined with other currently available treatment modalities, which seems to be an effective strategy to treat gastric cancer patients. In this review, we have summarized recent advances in gastric cancer treatment in terms of targeting EMT specifically, such as the administration of polyphenols, resveratrol, tangeretin, luteolin, genistein, proton pump inhibitors, terpenes, other plant extracts, or inorganic compounds.

Beyond the Mind-Serum Trace Element Levels in Schizophrenic Patients: A Systematic Review.

The alterations in serum trace element levels are common phenomena observed in patients with different psychiatric conditions such as schizophrenia, autism spectrum disorder, or major depressive disorder. The fluctuations in the trace element concentrations might act as potential diagnostic and prognostic biomarkers of many psychiatric and neurological disorders. This paper aimed to assess the alterations in serum trace element concentrations in patients with a diagnosed schizophrenia. The authors made a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 5009 articles identified through database searching, 59 of them were assessed for eligibility. Ultimately, 33 articles were included in the qualitative synthesis. This review includes the analysis of serum levels of the following trace elements: iron, nickel, molybdenum, phosphorus, lead, chromium, antimony, uranium, magnesium, aluminum, zinc, copper, selenium, calcium, and manganese. Currently, there is no consistency regarding serum trace element levels in schizophrenic patients. Thus, it cannot be considered as a reliable prognostic or diagnostic marker of schizophrenia. However, it can be assumed that altered concentrations of those elements are crucial regarding the onset and exaggeration of either psychotic or negative symptoms or cognitive dysfunctions.

Risk of Attacks by Blackflies (Diptera: Simuliidae) and Occurrence of Severe Skin Symptoms in Bitten Patients along the Eastern Border of the European Union.

The components of blackfly (Diptera: Simuliidae) saliva secreted during feeding on humans and animals induce various pathological reactions manifested by skin lesions and systemic symptoms. In this study, we describe 43 cases of severe skin lesions induced by blackfly bites and analyze their potential causes. Based on the results of a survey of 418 patients, we identified periods with risk of blackfly attacks and their environmental determinants in the eastern part of the European Union. Especially strong inflammatory reactions after blackfly bites were reported in patients with concomitant cardiovascular diseases (mainly with venous insufficiency), metabolic diseases, and bacterial infections. Enhanced symptoms of simuliosis were also observed in other patients attacked by these insects only once or repeatedly. The greatest number of blackfly attacks in the study area is recorded from May to July, with a peak in June (38.73%) in the afternoon (37.10%) and evening (33.03%), when patients are in fields, forests, or their households. The case analysis indicates interactions of various factors in the development of severe inflammatory reactions in patients bitten by blackflies. Therefore, it is recommended that subjects exposed to the presence of blackflies during their work or rest should limit the length of their stay in a vulnerable environment during the highest seasonal and daily activity of these insects. It is also necessary to take measures to reduce the number of blackflies and popularize methods for prophylaxis of their attacks.

Skin Lesions and Systemic Reactions in Humans Infested by Blackflies (Diptera: Simullidae) in Recreational Areas in Southeastern Poland.

Due to their mass occurrence in some environments and high aggressiveness, blackflies (Simulium spp.) represent the most bothersome arthropods attacking humans. In this study, we describe the medical effects of blackfly infestations in humans in southeastern Poland. Local and systemic reactions to blackfly bites were monitored in 418 patients (61.24% of females and 38.76% of males) of medical centers. Only skin lesions at the site of the bites were found in 88.52% of the patients, whereas accompanying systemic reactions were diagnosed in 11.48%. The most common signs observed in the area of the bites were pruritus (94.74%), burning (55.02%), edema (44.02%), and erythema (40.91%). The skin lesions, which were most often grouped small papules and papular and purpuric lesions with a varied range, typically persisted for several days, or for several weeks in some patients. Statistical analyses confirmed that the persistence of the skin lesions did not depend on the sex of the patients and the number of blackfly infestations. The systemic reactions to the components of the blackfly saliva were manifested by headache, increased body temperature, arthralgia, lymphadenopathy, and menstrual disorders in the females. The patients were most often attacked simultaneously by many blackflies on exposed parts of the body, mainly the upper limb, lower limb, head, and neck areas. The investigations indicate that blackflies are an important etiological factor of dermatitis and other symptoms in humans; hence, they should be considered in clinical diagnosis.

Gastric carcinogenesis: a comprehensive review of the angiogenic pathways.

Gastric cancer (GC) is undoubtedly one of the most prevalent malignancies worldwide. Since GC is the second leading cause of cancer-related deaths with nearly one million new diagnoses reported every year, there is a need for the development of new, effective treatment strategies of GC. Gastric carcinogenesis is a complex process that is induced by numerous factors and further stimulated by many pro-oncogenic pathways. Angiogenesis is the process of the new blood vessels formation from the already existing ones and it significantly contributes to the progression of gastric tumorigenesis and the growth of the cancerous tissues. The newly formed vessels provide cancer cells with proper nutrition, growth factors, and oxygen supply that are crucial for tumor growth and progression. Tumor-associated vessels differ from the physiological ones both morphologically and functionally. They are usually inefficient and unevenly distributed due to structural transformations. Thus, the development of the angiogenesis inhibitors that possess therapeutic effects has been the main focus of recent studies. Angiogenesis inhibitors mostly affect the vascular endothelial growth factor (VEGF) pathway since it is a major factor that stimulates the pro-angiogenic pathways. The aim of this review was to describe and summarize other promising molecular pathways that might be crucial in further improvements in GC therapies. This article provides an overview of how a meaningful role in tumor progression the angiogenetic process has. Furthermore, this review includes a description of the most important angiogenic factors as well as pathways and their involvement in gastric carcinogenesis.

Treatment Strategies of Gastric Cancer-Molecular Targets for Anti-angiogenic Therapy: a State-of-the-art Review.

PURPOSE: Recent studies have suggested that molecular targets for the anti-angiogenic therapy might constitute a basis for additional therapy in gastric cancer treatment. A vast number of molecules, receptors, pathways, specific interactions, and thus strategies that target gastric cancer angiogenesis specifically have been reported in numerous research articles and clinical trials. METHODS: We conducted a systematic literature review of molecularly targeted treatment strategies in gastric cancer on the following databases-PubMed, Google Scholar, and Scopus-on September 20, 2020. Multiple articles and evaluations were searched for studies reporting newly found and promising molecular anti-angiogenic therapy pathways. Eventually, 39 articles regarding the anti-angiogenic therapy in gastric cancer were included in the final analysis. RESULTS: As a consequence of the release of the pro-angiogenic molecules from the tumour cells, gastric cancer presents high angiogenic capability. Therefore, potential schemes for future treatment strategies include the decrease of the process ligands as well as the expression of their receptors. Moreover, the increase in the angiogenic inhibitor levels and direct aim for the inner walls of the endothelial cells appear as a promising therapeutic strategy. Beyond that, angiogenesis process inhibition seems to indirectly exaggerate the effects of chemotherapy in the considered patients. CONCLUSIONS: The anti-angiogenic treatment in gastric cancer patients evaluates its significance especially in the early stages of the malignancy. The studies conducted so far show that most of the meaningful angiogenic factors and receptors with the potential molecular pathways should be further evaluated since they could potentially play a substantial role in future therapies.

Viral Infections in Burn Patients: A State-Of-The-Art Review.

Infections that are triggered by the accompanying immunosuppression in patients with burn wounds are very common regardless of age. Among burn patients, the most frequently diagnosed infections include the bacterial ones primarily caused by Pseudomonas aeruginosa or Klebsiella pneumonia, as well as fungal infections with the etiology of Candida spp. or Aspergillus spp. Besides, burn wounds are highly susceptible to viral infections mainly due to the impaired immune responses and defective functions of the immune cells within the wound microenvironment. The most prevalent viruses that invade burn wounds include herpes simplex virus (HSV), cytomegalovirus (CMV), human papilloma virus (HPV), and varicella zoster virus (VZV). Likewise, less prevalent infections such as those caused by the orf virus or Epstein-Barr Virus (EBV) might also occur in immunosuppressed burn patients. Viral infections result in increased morbidity and mortality rates in severely burned patients. Additionally, a positive correlation between the hospitalization duration and the severity of the viral infection has been demonstrated. Viral infections trigger the occurrence of various complications, ranging from mild symptoms to even fatal incidents. Accurate detection of viral infection is of great clinical importance because of the possibility for a quicker introduction of proper treatment therapy and shortening of hospitalization time. The aim of this paper is to provide a comprehensive review of the literature and summarize the findings regarding the most common viral infections in immunosuppressed burn patients.

Helicobacter pylori Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment.

Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.

State of the art for gastric signet ring cell carcinoma: from classification, prognosis, and genomic characteristics to specified treatments.

Gastric cancer (GC) is responsible for 9% of cancer deaths worldwide. Over 950,000 new cases are diagnosed each year, and about 90% of them are in advanced stage, requiring chemotherapy. In Europe there has been research based on pre- and postoperative chemotherapy treatment, using 5-fluorouracil, epirubicin, cisplatin, capecitabine, and docetaxel. Chemotherapy significantly impairs the quality of life of patients; however, the final effects are not always satisfactory. There is scientific evidence that gastric mucus tumors and signet ring cell carcinomas have a pattern of specific signatures, that distinguish them from other gastric cancer subtypes, and may be associated with a poor response to systematic treatment. Signet ring cell carcinoma is less chemosensitive than others, and the increase in the percentage of signet ring cells correlates with resistance to chemotherapy. Perioperative chemotherapy in advanced signet ring cell carcinomas is an independent factor of poor prognosis and survival, which is explained by the toxicity of neoadjuvant treatment. Therefore, curative surgical resection enhanced by standardized lymphadenectomy remains the recommended gold standard in GC therapy. According to presented studies, early detection and aggressive treatments for this subtype of GC is a reasonable approach. This review paper is mostly addressed to physicians who are interested in updating to the state of the art concerning different subtypes of gastric carcinoma.

Intra-manufacture Diameter Variability of Rotary Files and Their Corresponding Gutta-Percha Cones Using Laser Scan Micrometre.

INTRODUCTION: Manufacturers offer gutta-percha (GP) cones matched with different sizes of endodontic files as an attempt to simplify the obturation process and create a tight seal in the canal. The purpose of this study was to evaluate whether intra-manufacture GP diameters matched the diameters of their corresponding files at different levels using laser micrometre. METHODS AND MATERIALS: Twenty files and corresponding GP master cones of Reciproc R40 (40/0.06) (VDW, Munich, Germany), WaveOne Large(40/0.08)(Dentsply Maillefer, Ballaigues, Switzerland), ProTaper F3 (30/0.09) (Dentsply Maillefer, Ballaigues, Switzerland), and Mtwo 40/0.06 (VDW, Munich, Germany) were examined using laser micrometre (LSM 6000 by Mitutoyo, Japan) with accuracy of 1 nm to establish their actual diameter at D0, D1, D3 and D6. The data was analysed using the independent t-test. The differences were considered at 0.05. RESULTS: The diameter of GP master cones was significantly larger than that of the corresponding files at all levels in all brands. ProTaper GP diameter was closest to the file diameter at D1 (GP=0.35, File=0.35 mm), and D3 (GP=0.48, File=0.49). CONCLUSION: Within the same manufacturer, GP cone diameters do not match the diameters of their corresponding files. Clinicians are advised to use a GP gauge to cut the tip so as to appropriate the diameter from a smaller sized GP cone.

The Intra-Manufacture Diameter Variability of Rotary Files and Their Corresponding Gutta-Percha Cones Using Laser Scan Micrometer.

Introduction: As an attempt to simplify the obturation process and create a tight seal, manufacturers offer gutta-percha (GP) cones matching different sizes of endodontic files. The purpose of this study was to evaluate whether intra-manufacture GP diameters matched the diameters of their corresponding files at different horizontal levels of the canal. Methods and Materials: Twenty files and corresponding GP master cones of Reciproc R 40/0.08 (VDW, Munich, Germany), WaveOne Large (40/0.08) (Dentsply Maillefer, Ballaigues, Switzerland), ProTaper F3 (30/0.09) (Dentsply Maillefer, Ballaigues, Switzerland), and Mtwo (40/0.06) (VDW, Munich, Germany) were examined using laser micrometer (LSM 6000 by Mitutoyo, Japan) with accuracy of 1 nm to establish their actual diameter at D0, D1, D3 and D6. Data were analysed using the independent t-test. The differences were considered as significant for P<0.05. Results: The diameter of GP master cones was significantly larger than the corresponding files at all levels with all the above brands. ProTaper GP diameter were closest to the file diameter at D1 (GP=0.35, File=0.35 mm), and D3 (GP=0.48, file=0.49). Conclusion: This in vitro study showed that within the same manufacturer GP cone diameters do not match the diameters of their corresponding files.

[The public health risk of ticks and tick-borne diseases in the south-eastern Poland]. / Stopien zagrozenia mieszkaniców Poludniowo-Wschodniej Polski kleszczami i chorobami odkleszczowymi.

The aim of the study was to estimate risk of tick-borne diseases among inhabitants of Lublin macroregion. The incidence of Lyme disease in the residents of Lubelskie Voivodeship increased from 2.9 to 6.3 in the period between 2002 and 2003. In 16% of patients studied there were systemic reactions observed after tick bite, while the local symptoms were noted in 56% of bitten subjects. Our data indicates that 59% of the respondents have poor knowledge of ticks and tic-borne diseases.

Tick bites on humans in the agricultural and recreational areas in south-eastern Poland.

The investigations were conducted in the Lublin province (south-eastern Poland) in areas of high agricultural and recreational value. Among the 418 patients admitted to medical clinics due to arthropod bites in the years 2003-2005, 184 people (44%) had been bitten by ticks. As shown by the research, high-risk groups include people whose stay in tick habitats is connected with their occupational work (54.5%) as well as recreation and tourism (45.5%). As many as 78.7% of the patients were attacked by Ixodes ricinus ticks in forests, and much fewer (31.3%) in other habitats located in urban and rural areas. In one case, a Dermacentor reticulatus female was attached to the skin. Ticks were most commonly located on the upper (28.8%) and lower (27.2%) extremities, and on the abdomen (15.8%). Local skin reactions (57.6%) with predominance of erythema were the most prevalent. Combined local and systemic symptoms were reported less frequently (20.1%). The general symptoms were headache (10.8% of patients), fever (5.4%), lymphadenitis (5.9%) and arthralgia (4.3%). No lesions produced by tick bites were reported in 22.3% of the patients. Field studies conducted in 2003-2004 demonstrated that I. ricinus is a common species in the southern part of the Lublin province, where the density of nymphs and adult forms in various localities during the period of peak seasonal activity (in May) ranges from 18.5-26 specimens/1 h of collection. Two tick species, I. ricinus and D. reticulatus, occur in the northern part of the province. The density of I. ricinus nymphs and adult forms as well as D. reticulatus adults is in the range of 2.5-42 specimens/1 hr of collection and 19.5-64.0 speciments/1 hr of collection, respectively. Due to the high risk of tick attacks in the study area, there arises the necessity to permanent the monitoring of ticks numbers and tick-borne diseases.