Malignant ureteral obstruction can result in renal dysfunction or urosepsis and can limit the physician’s ability to treat the underlying cancer.There are multiple methods to deal with ureteral obstruction including ...Malignant ureteral obstruction can result in renal dysfunction or urosepsis and can limit the physician’s ability to treat the underlying cancer.There are multiple methods to deal with ureteral obstruction including regular polymeric double J stents(DJS),tandem DJS,nephrostomy tubes,and then more specialized products such as solid metal stents(e.g.,Resonance Stent,Cook Medical)and polyurethane stents reinforced with nickel-titanium(e.g.,UVENTA stents,TaeWoong Medical).In patients who require long-term stenting,a nephrostomy tube could be transformed subcutaneously into an extra-anatomic stent that is then inserted into the bladder subcutaneously.We outline the most recent developments published since 2012 and report on identifiable risk factors that predict for failure of urinary drainage.These failures are typically a sign of cancer progression and the natural history of the disease rather than the individual type of drainage device.Factors that were identified to predict drainage failure included low serum albumin,bilateral hydronephrosis,elevated C-reactive protein,and the presence of pleural effusion.Head-to-head studies show that metal stents are superior to polymeric DJS in terms of maintaining patency.Discussions with the patient should take into consideration the frequency that exchanges will be needed,the need for externalized hardware(with nephrostomy tubes),or severe urinary symptoms in the case of internal DJS.This review will highlight the current state of diversions in the setting of malignant ureteral obstruction.展开更多
BACKGROUND The spread of the severe acute respiratory syndrome coronavirus 2 outbreak worldwide has caused concern regarding the mortality rate caused by the infection.The determinants of mortality on a global scale c...BACKGROUND The spread of the severe acute respiratory syndrome coronavirus 2 outbreak worldwide has caused concern regarding the mortality rate caused by the infection.The determinants of mortality on a global scale cannot be fully understood due to lack of information.AIM To identify key factors that may explain the variability in case lethality across countries.METHODS We identified 21 Potential risk factors for coronavirus disease 2019(COVID-19)case fatality rate for all the countries with available data.We examined univariate relationships of each variable with case fatality rate(CFR),and all independent variables to identify candidate variables for our final multiple model.Multiple regression analysis technique was used to assess the strength of relationship.RESULTS The mean of COVID-19 mortality was 1.52±1.72%.There was a statistically significant inverse correlation between health expenditure,and number of computed tomography scanners per 1 million with CFR,and significant direct correlation was found between literacy,and air pollution with CFR.This final model can predict approximately 97%of the changes in CFR.CONCLUSION The current study recommends some new predictors explaining affect mortality rate.Thus,it could help decision-makers develop health policies to fight COVID-19.展开更多
Background:Muscular strength is an important component of physical fitness.We evaluated the relationship between baseline muscular strength and risk of stroke among adults who were aged≥65 years during follow-up.Meth...Background:Muscular strength is an important component of physical fitness.We evaluated the relationship between baseline muscular strength and risk of stroke among adults who were aged≥65 years during follow-up.Methods:We included 7627 healthy adults(mean age=43.9 years,86.0%male)underwent a baseline physical examination between 1980 and 1989.Muscular strength was determined by 1-repetition maximum measures for bench press and leg press and categorized into age-and sex-specific tertiles for each measure.Cardiorespiratory fitness(CRF)was assessed via a maximal treadmill exercise test.Those enrolled in fee-for-service Medicare from 1999 to 2019 were included in the analyses.Associations between baseline strength and stroke outcomes were estimated using a modified Cox proportional hazards model.In a secondary analysis,we examined stroke risk by categories of CRF where Quintile 1=low,Quintiles 2-3=moderate,and Quintiles 4-5=high CRF based on age and sex.Results:After 70,072 person-years of Medicare follow-up,there were 1211 earliest indications of incident stroke.In multivariable analyses,the hazard ratio(95%confidence interval(95%CI))for stroke across bench press categories were 1.0(referent),0.96(0.83-1.11),and 0.89(0.77-1.04),respectively(p trend=0.14).The trend across categories of leg press was also non-significant(p trend=0.79).Adjusted hazard ratio(95%CI)for stroke across ordered CRF categories were 1.0(referent),0.90(0.71-1.13),and 0.72(0.57-0.92)(p trend<0.01).Conclusion:While meeting public health guidelines for muscular strengthening activities is likely to improve muscular strength as well as many health outcomes in older adults,performing such activities may not be helpful in preventing stroke.Conversely,meeting guidelines for aerobic activity is likely to improve CRF and lower stroke risk.展开更多
Silver dendritic nanonstructures obtained by the potentiostatic electrolysis from different electrolytes at different overpotentials were characterized by the scanning electron microscopy(SEM)technique and X-ray diffr...Silver dendritic nanonstructures obtained by the potentiostatic electrolysis from different electrolytes at different overpotentials were characterized by the scanning electron microscopy(SEM)technique and X-ray diffraction analysis of the produced particles.The needle-like and fern-like dendrites were formed from the nitrate electrolyte at overpotentials inside and outside plateaus of the limiting diffusion current density,respectively.The three-dimensional pine-like dendrites constructed from approximately spherical grains were formed from the ammonium electrolyte at overpotentials both inside and outside plateaus of the limiting diffusion current density.The morphology of silver dendrites was correlated with their crystal structure at the semi quantiative level.The change of crystal orientation from the strong(111)preferred orientation for the needle-like dendrites to almost randomly orientied spherical grains in the pine-like dendrites obtained at the overpotential outside the plateau of the limiting diffusion current density was observed.This trend in change of crystal orientation and morphology of Ag nanostructures was accompanied by considerable increase of the specific surface area(SSA)of the produced powders.The average crystallite sizes were in the range of 38-50 nm,proving nanostructural character of the formed Ag particles.展开更多
Exosomes derived from mesenchymal stem cells(MSC-Exos)are nano-sized extracellular vesicles enriched with bioactive molecules,such as microRNAs,enzymes,cytokines,chemokines,immunomodulatory,trophic,and growth factors....Exosomes derived from mesenchymal stem cells(MSC-Exos)are nano-sized extracellular vesicles enriched with bioactive molecules,such as microRNAs,enzymes,cytokines,chemokines,immunomodulatory,trophic,and growth factors.These molecules regulate the survival,phenotype,and function of malignant and tumor-infiltrated immune cells.Due to their nano-size and bilayer lipid envelope,MSC-Exos can easily bypass biological barriers and may serve as drug carriers to deliver chemotherapeutics directly into the tumor cells.Here,we summarize current knowledge regarding molecular mechanisms responsible for MSC-Exos-dependent modulation of tumor progression and discuss insights regarding the therapeutic potential of MSC-Exos in the treatment of malignant diseases.展开更多
Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents ...Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma treatment.Methods: Expression of AGTR1 and PPARγ m RNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method.Results: Both AGTR1 and PPARγ mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell apoptosis.Increased glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the treatment.Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression.展开更多
Acute liver failure(ALF)is a severe and life-threatening condition in which rapid deterioration of liver function develops in a patient who has no preexisting liver disease.Mesenchymal stem cells(MSCs)are immunoregula...Acute liver failure(ALF)is a severe and life-threatening condition in which rapid deterioration of liver function develops in a patient who has no preexisting liver disease.Mesenchymal stem cells(MSCs)are immunoregulatory stem cells which are able to modulate phenotype and function of all immune cells that play pathogenic role in the development and progression of ALF.MSCs in juxtacrine and paracrine manner attenuate antigen-presenting properties of dendritic cells and macrophages,reduce production of inflammatory cytokines in T lymphocytes,suppress hepatotoxicity of natural killer T(NKT)cells and promote generation and expansion of immunosuppressive T,B and NKT regulatory cells in acutely inflamed liver.Due to their nano-sized dimension and lipid envelope,intravenously injected MSC-derived exosomes(MSC-Exos)may by-pass all biological barriers to deliver MSC-sourced immunoregulatoy factors directly into the liver-infiltrated immune cells and injured hepatocytes.Results obtained by us and others revealed that intravenous administration of MSCs and MSC-Exos efficiently attenuated detrimental immune response and acute inflammation in the liver,suggesting that MSCs and MSC-Exos could be considered as potentially new remedies in the immunotherapy of ALF.In this review,we emphasize the current knowledge about molecular and cellular mechanisms which are responsible for MSC-based modulation of liver-infiltrated immune cells and we discuss different insights regarding the therapeutic potential of MSCs in liver regeneration.展开更多
BACKGROUND Rectal cancer(RC)is one of the most common diagnosed cancers,and one of the major causes of cancer-related death nowadays.Majority of the current guidelines rely on TNM classification regarding therapy regi...BACKGROUND Rectal cancer(RC)is one of the most common diagnosed cancers,and one of the major causes of cancer-related death nowadays.Majority of the current guidelines rely on TNM classification regarding therapy regiments,however recent studies suggest that additional histopathological findings could affect the disease course.AIM To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival(OS)of RC patients.METHODS A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic,Clinical Center of Serbia,between the years of 2014–2016.All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification.In addition,the patient’s demographics,surgical details,postoperative pathological details,differentiation degree and their correlation with OS was investigated.RESULTS Of 245 included patients with stage Ⅰ-Ⅲ RC,lymphovascular invasion(LVI)was identified in 92 patients(38%),whereas perineural invasion(PNI)was present in 46 patients(19%).Using Kaplan-Meier analysis for overall survival rate,we have found that both LVI and PNI were associated with lower survival rates(P<0.01).Moreover when Cox multiple regression model was used,LVI,PNI,older age,male gender were predictors of poor prognosis(HR=5.49;95%CI:2.889-10.429;P<0.05).CONCLUSION LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients,hence more aggressive therapy should be reserved for these patients after curative resection.展开更多
Compliant mechanisms transfer an input force or displacement to another point through elastic body deformation. The field of compliant mechanisms is expected to continue to grow as materials with superior properties a...Compliant mechanisms transfer an input force or displacement to another point through elastic body deformation. The field of compliant mechanisms is expected to continue to grow as materials with superior properties are developed. The paper takes into consideration some typical spring guiding systems, being able to realize translating planar displacement of the link. Some types of compound spring guiding systems, such as S-shaped guiding spring system, U-shaped guiding spring system and four spring guiding system with additional rigid-body link have been considered and analyzed as compliant structures. The mobility as well as guiding accuracy of the developed compliant mechanisms, that is, their capability to realize translating planar displacement of the link, have been researched, and the optimal dimensions of the mechanism have been determined in order to provide minimal guiding inaccuracy.展开更多
Celiac disease(CD) is a common and well defined autoimmune disorder caused by gliadin and related proteins of wheat,rye,and barley.Epidemiologic studies confirmed that CD is highly associated with other autoimmune dis...Celiac disease(CD) is a common and well defined autoimmune disorder caused by gliadin and related proteins of wheat,rye,and barley.Epidemiologic studies confirmed that CD is highly associated with other autoimmune diseases and with Down syndrome(DS).The symptomatic form of CD in patients with DSis more frequent than asymptomatic forms.However,growth impairment,anemia,intermittent diarrhea,and constipation are symptoms and signs typically of children with DS without CD.Late identification of the disease can lead to various complications,sometimes even very severe.Therefore,systematic screening for CD is essential in the management of children and adolescents with DS.Many medical organizations recommend screening in this group of patients.However,current policy statements vary in their recommendations for screening and there is still a need for establishing uniform diagnostic criteria.展开更多
Energy sector represents a key industrial branch for national, environmental and economic success. With its exclusive access to domestic deposits, lignite industry represents a guarantor of reliable raw materials, off...Energy sector represents a key industrial branch for national, environmental and economic success. With its exclusive access to domestic deposits, lignite industry represents a guarantor of reliable raw materials, offering long-term supply security based on verified reserves. Currently operated coalmines in Serbia (Kolubara and Kostolac) have production around 36 million tons of lignite, and over 108 million m3 of overburden. Consequently, sustainability of lignite production requires cost reduction and environmental protection, as well as capacity increase. In order to rationalise, and increase efficiency of Serbian lignite mines, it is necessary to focus the activities on major issues shown within the triangle of energy policy objectives (security of supply, competi- tive prices and environmental protection). Production process optimisation singled out several special programs. Equipment revi- talization and modernization is necessary taking into account that majority of the currently operated machinery has a life up to 25 years. Production process automation would enable high level of technical operation in the field of open cast mines management. Lack of coal quality uniformity is the permanent problem resulting by great amounts of coal reserves to be used uneconomically. Planning and training at all levels and finally cooperative software for business procedures and work order management. The measures suggested are a key precondition for maintaining competitive position of lignite production on international level.展开更多
AIMTo establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG).METHODSOur study included 120 patients ...AIMTo establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG).METHODSOur study included 120 patients who were referred for cataract surgery. All patients were divided into four groups according to clinical findings: XFG, early and late pseudoexfoliation syndrome (XFS), and cataract (without pseudoexfoliation). Serum and aqueous humour levels of the ascorbic acid, NO and TNF-α were measured. The concentrations of the ascorbic acid and NO were measured by an appropriate spectrophotometric method. Enzyme-linked immunosorbent assay (ELISA) was used to determine TNF-α level.RESULTSAqueous humour concentration of ascorbic acid was significantly lower in patients with late XFS (0.61±0.11 mmol/L) and XFG (0.48±0.15 mmol/L) compared to patients with early XFS (0.9±0.15 mmol/L) and cataract (1.16±0.22 mmol/L), while there was no difference in serum concentration in all examined groups. Aqueous humour concentration of NO was significantly higher in patients with XFG (77.7±11.4 µmol/L) compared to patients with early XFS (50.27±9.34 µmol/L) and cataract (49.77±7.1 µmol/L), while serum concentration was increased in the early stage of XFS (73.26±8.29 µmol/L). Aqueous humour level of proinflammatory cytokine TNF-α was increased in patients with XFS (early 460.04±18.32 pg/mL; late 502.42±53.23 pg/mL) and XFG (510.34±43.07 pg/mL), while there was no difference in serum level in all examined groups of patients.CONCLUSIONReduced ascorbic acid and elevated NO and inflammation related cytokine TNF-α level in aqueous humour of the patients with developed XFG suggest that oxidative stress induces local inflammation.展开更多
AIM： To evaluate the clinical characteristics of splenic marginal-zone lymphoma （SMZL） following antigen expression and the influence of therapeutic approaches on clinical outcome and overall survival （OS）.METHOD...AIM： To evaluate the clinical characteristics of splenic marginal-zone lymphoma （SMZL） following antigen expression and the influence of therapeutic approaches on clinical outcome and overall survival （OS）.METHODS： A total of 30 patients with typical histological and immunohistochemical SMZL patterns were examined. Splenectomy plus chemotherapy was applied in 20 patients, while splenectomy as a single treatment-option was performed in 10 patients. Prognostic factor and overall survival rate were analyzed.RESULTS： Complete remission （CR） was achieved in 20 （66.7%）, partial remission （PR） in seven （23.3%）, and lethal outcome due to disease progression occurred in three （10.0%） patients. Median survival of patients with a splenectomy was 93.0 mo and for patients with splenectomy plus chemotherapy it was 207.5 mo （Log rank = 0.056, P 〉 0.05）. Time from onset of first symptoms to the beginning of the treatment （mean 9.4 too） was influenced by spleen dimensions, as measured by computerized tomography and ultra-sound （t = 2.558, P = 0.018）. Strong positivity （＋＋＋） of CD20 antigen expression in splenic tissue had a positive influence on OS （Log rank = 5.244, P 〈 0.05）. The analysis of factors interfering with survival （by the Kaplan-Meier method） revealed that gender, general symptoms, clinical stage, and spleen infiltration type （nodular vs diffuse） had no significant （P 〉 0.05） effects on the OS. The expression of other antigens （immunohistochemistry） also had no effect on survival-rate, as measured by a χ^2 test （P 〉 0.05）.CONCLUSION： Initial splenectomy combined with chemotherapy has been shown to be beneficial due to its advanced remission rate/duration; however, a larger controlled clinical study is required to confirm our findings.展开更多
Background:We examined the associations of cardiorespiratory fitness(CRF) and white blood cell count(WBC) with mortality outcomes.Methods: A total of 52,056 apparently healthy adults completed a comprehensive health e...Background:We examined the associations of cardiorespiratory fitness(CRF) and white blood cell count(WBC) with mortality outcomes.Methods: A total of 52,056 apparently healthy adults completed a comprehensive health examination,including a maximal treadmill test and blood chemistry analyses.CRF was categorized as high,moderate,or low by age and sex;WBC was categorized as sex-specific quartiles.Results:During 17.8± 9.5 years(mean± SD) of follow-up,a total of 4088 deaths occurred.When regressed jointly,significantly decreased allcause mortality across CRF categories was observed within each quartile of WBC in men.Within WBC Quartile 1,all-cause mortality hazard ratios(HRs) with a 95% confidence interval(95%CI) were 1.0(referent),1.29(95%CI:1.06-1.57),and 2.03(95%CI:1.42-2.92) for high,moderate,and low CRF categories,respectively(p for trend <0.001).Similar trends were observed in the remaining 3 quartiles.With the exception of cardiovascular disease(CVD) mortality within Quartile 1(p for trend=0.743),there were also similar trends across CRF categories within WBC quartiles in men for both CVD and cancer mortality(p for trend <0.01 for all).For women,there were no significant trends across CRF categories for mortality outcomes within Quartiles 1-3.However,we observed significantly decreased all-cause mortality across CRF categories within WBC Quartile 4(HR=1.05(95%CI:0.76-1.44),HR=1.63(95%CI:1.20-2.21),and HR=1.87(95%CI:1.29-2.69) for high,moderate,and low CRF,respectively(p for trend=0.002)).Similar trends in women were observed for CVD and cancer mortality within WBC Quartile 4 only.Conclusion:There are strong joint associations between CRF,WBC,and all-cause,CVD,and cancer mortality in men;these associations are less consistent in women.展开更多
Charles Darwin was deeply interested in carnivorous plants and was particularly fascinated by Venus flytrap(Dionaea muscipula)and sundew plants(Drosera spp.)of the Droseraceae family.He was intrigued by fast and slow ...Charles Darwin was deeply interested in carnivorous plants and was particularly fascinated by Venus flytrap(Dionaea muscipula)and sundew plants(Drosera spp.)of the Droseraceae family.He was intrigued by fast and slow trap movements in these plants and predicted the existence of a signal that transfers information from sensor to actuator within the trap organ.Based on his request,Sir John Burdon-Sanderson discovered electrical signals in Venus flytrap.Recent success in the transformation of non-model carnivorous plants with a Ca2+sensor has outlined a possible route for the evolution of sensory systems in the carnivorous family Droseraceae.展开更多
BACKGROUND Neuroendocrine tumors of appendix(ANETs)known as carcinoids,are rare endocrine neoplasms originated from enterochromaffin cells of gastrointestinal tract.ANETs are the third most frequent(16.7%)gastrointest...BACKGROUND Neuroendocrine tumors of appendix(ANETs)known as carcinoids,are rare endocrine neoplasms originated from enterochromaffin cells of gastrointestinal tract.ANETs are the third most frequent(16.7%)gastrointestinal neuroendocrine tumors,with the incidence of 0.08-0.2 cases/100000 during one year.Incidental ANETs occur in 0.2%-0.7%of emergency surgical resections because of suspected appendicitis which is usually the first manifestation of ANET.Although there are a lot of papers about application of somatostatin receptor scintigraphy in gastrointestinal neuroendocrine tumors,there are very rare sporadic cases described about ANETs particularly.AIM To establish the role of somatostatin receptor scintigraphy(SRS)in the management of patients with neuroendocrine tumors of appendix(ANET).METHODS The total of 35 patients was investigated,23 females and 12 males,average age(43.7±17.3 years).All patients had histological diagnosis of ANET(34 carcinoids of appendix and one tubular carcinoid).Majority of tumors have been found incidentally during surgery of:Acute appendicitis(n=15),perforated appendicitis(n=2),ileus(n=3),hysterectomy(n=3),ruptured ovarian cyst(n=2),caecal volvulus(n=1),while 9 patients had diagnosis of appendiceal tumor before the surgery.Seventeen patients had tumor grade(G)G1,12 G2 and 6 G3.The right hemicolectomy was performed in 13,while the rest of the patients had appendectomy only.SRS was done early(2 h)and late(24 h)after i.v.application of 740 MBq technetium-99 m ethylenediamine-N,N’-diacetic acid Hydrazinonicotinyl-Tyr3-Octreotide(technetium-99 m-Tektrotyd,Polatom,Poland).SRS was performed for restaging in all the patients after surgery.RESULTS There were 12 true positive(TP),19 true negative,3 false positive and 1 false negative SRS result.Sensitivity of the method was 92.31%,specificity was 86.36%,positive predictive value was 80.00%,negative predictive value was 95.00%and accuracy 88.57%.Receiver operating characteristics analysis showed that SRS scintigraphy is a good test for detec展开更多
Detrimental immune response has a crucially important role in the development and progression of inflammatory eye diseases.Inflammatory mediators and proteolytic enzymes released by activated immune cells induce serio...Detrimental immune response has a crucially important role in the development and progression of inflammatory eye diseases.Inflammatory mediators and proteolytic enzymes released by activated immune cells induce serious injury of corneal epithelial cells and retinal ganglion cell which may result in the vision loss.Mesenchymal stem cells(MSCs)are regulatory cells which produce various immunosuppressive factors that modulate phenotype and function of inflammatory immune cells.However,several safety issues,including undesired differentiation and emboli formation,limit clinical use of MSCs.MSC-derived exosomes(MSC-Exos)are nano-sized extracellular vesicles which contain all MSC-derived immunoregulatory factors.Intraocular administration of MSCExos efficiently attenuated eye inflammation and significantly improved visual acuity in experimental animals without causing any severe side effects.As cell-free product,MSC-Exos addressed all safety issues related to the transplantation of MSCs.Therefore,MSC-Exos could be considered as potentially new remedy for the treatment of inflammatory eye diseases which efficacy should be explored in up-coming clinical trials.展开更多
Planning and production optimization within multiple mines or several work sites （entities） mining systems by using fuzzy linear programming （LP） was studied. LP is the most commonly used operations research metho...Planning and production optimization within multiple mines or several work sites （entities） mining systems by using fuzzy linear programming （LP） was studied. LP is the most commonly used operations research methods in mining engineering. After the introductory review of properties and limitations of applying LP, short reviews of the general settings of deterministic and fuzzy LP models are presented. With the purpose of comparative analysis, the application of both LP models is presented using the example of the Bauxite Basin Niksic with five mines. After the assessment, LP is an efficient mathematical modeling tool in production planning and solving many other single-criteria optimization problems of mining engineering. After the comparison of advantages and deficiencies of both deterministic and fuzzy LP models, the conclusion presents benefits of the fuzzy LP model but is also stating that seeking the optimal plan of production means to accomplish the overall analysis that will encompass the LP model approaches.展开更多
文摘Malignant ureteral obstruction can result in renal dysfunction or urosepsis and can limit the physician’s ability to treat the underlying cancer.There are multiple methods to deal with ureteral obstruction including regular polymeric double J stents(DJS),tandem DJS,nephrostomy tubes,and then more specialized products such as solid metal stents(e.g.,Resonance Stent,Cook Medical)and polyurethane stents reinforced with nickel-titanium(e.g.,UVENTA stents,TaeWoong Medical).In patients who require long-term stenting,a nephrostomy tube could be transformed subcutaneously into an extra-anatomic stent that is then inserted into the bladder subcutaneously.We outline the most recent developments published since 2012 and report on identifiable risk factors that predict for failure of urinary drainage.These failures are typically a sign of cancer progression and the natural history of the disease rather than the individual type of drainage device.Factors that were identified to predict drainage failure included low serum albumin,bilateral hydronephrosis,elevated C-reactive protein,and the presence of pleural effusion.Head-to-head studies show that metal stents are superior to polymeric DJS in terms of maintaining patency.Discussions with the patient should take into consideration the frequency that exchanges will be needed,the need for externalized hardware(with nephrostomy tubes),or severe urinary symptoms in the case of internal DJS.This review will highlight the current state of diversions in the setting of malignant ureteral obstruction.
文摘BACKGROUND The spread of the severe acute respiratory syndrome coronavirus 2 outbreak worldwide has caused concern regarding the mortality rate caused by the infection.The determinants of mortality on a global scale cannot be fully understood due to lack of information.AIM To identify key factors that may explain the variability in case lethality across countries.METHODS We identified 21 Potential risk factors for coronavirus disease 2019(COVID-19)case fatality rate for all the countries with available data.We examined univariate relationships of each variable with case fatality rate(CFR),and all independent variables to identify candidate variables for our final multiple model.Multiple regression analysis technique was used to assess the strength of relationship.RESULTS The mean of COVID-19 mortality was 1.52±1.72%.There was a statistically significant inverse correlation between health expenditure,and number of computed tomography scanners per 1 million with CFR,and significant direct correlation was found between literacy,and air pollution with CFR.This final model can predict approximately 97%of the changes in CFR.CONCLUSION The current study recommends some new predictors explaining affect mortality rate.Thus,it could help decision-makers develop health policies to fight COVID-19.
文摘Background:Muscular strength is an important component of physical fitness.We evaluated the relationship between baseline muscular strength and risk of stroke among adults who were aged≥65 years during follow-up.Methods:We included 7627 healthy adults(mean age=43.9 years,86.0%male)underwent a baseline physical examination between 1980 and 1989.Muscular strength was determined by 1-repetition maximum measures for bench press and leg press and categorized into age-and sex-specific tertiles for each measure.Cardiorespiratory fitness(CRF)was assessed via a maximal treadmill exercise test.Those enrolled in fee-for-service Medicare from 1999 to 2019 were included in the analyses.Associations between baseline strength and stroke outcomes were estimated using a modified Cox proportional hazards model.In a secondary analysis,we examined stroke risk by categories of CRF where Quintile 1=low,Quintiles 2-3=moderate,and Quintiles 4-5=high CRF based on age and sex.Results:After 70,072 person-years of Medicare follow-up,there were 1211 earliest indications of incident stroke.In multivariable analyses,the hazard ratio(95%confidence interval(95%CI))for stroke across bench press categories were 1.0(referent),0.96(0.83-1.11),and 0.89(0.77-1.04),respectively(p trend=0.14).The trend across categories of leg press was also non-significant(p trend=0.79).Adjusted hazard ratio(95%CI)for stroke across ordered CRF categories were 1.0(referent),0.90(0.71-1.13),and 0.72(0.57-0.92)(p trend<0.01).Conclusion:While meeting public health guidelines for muscular strengthening activities is likely to improve muscular strength as well as many health outcomes in older adults,performing such activities may not be helpful in preventing stroke.Conversely,meeting guidelines for aerobic activity is likely to improve CRF and lower stroke risk.
基金supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia under the research project: “Electrochemical synthesis and characterization of nanostructured functional materials for application in new technologies” (Project No. 172046)
文摘Silver dendritic nanonstructures obtained by the potentiostatic electrolysis from different electrolytes at different overpotentials were characterized by the scanning electron microscopy(SEM)technique and X-ray diffraction analysis of the produced particles.The needle-like and fern-like dendrites were formed from the nitrate electrolyte at overpotentials inside and outside plateaus of the limiting diffusion current density,respectively.The three-dimensional pine-like dendrites constructed from approximately spherical grains were formed from the ammonium electrolyte at overpotentials both inside and outside plateaus of the limiting diffusion current density.The morphology of silver dendrites was correlated with their crystal structure at the semi quantiative level.The change of crystal orientation from the strong(111)preferred orientation for the needle-like dendrites to almost randomly orientied spherical grains in the pine-like dendrites obtained at the overpotential outside the plateau of the limiting diffusion current density was observed.This trend in change of crystal orientation and morphology of Ag nanostructures was accompanied by considerable increase of the specific surface area(SSA)of the produced powders.The average crystallite sizes were in the range of 38-50 nm,proving nanostructural character of the formed Ag particles.
基金supported by the European Crohn’s and Colitis Organization(ECCO)(Grant“The Role of Galectin 3 in Acute Colitis”)Serbian Ministry of Science(Grant Nos.ON175069 and ON175103),Faculty of Medical Sciences University of Kragujevac(Grant No.MP01/18).
文摘Exosomes derived from mesenchymal stem cells(MSC-Exos)are nano-sized extracellular vesicles enriched with bioactive molecules,such as microRNAs,enzymes,cytokines,chemokines,immunomodulatory,trophic,and growth factors.These molecules regulate the survival,phenotype,and function of malignant and tumor-infiltrated immune cells.Due to their nano-size and bilayer lipid envelope,MSC-Exos can easily bypass biological barriers and may serve as drug carriers to deliver chemotherapeutics directly into the tumor cells.Here,we summarize current knowledge regarding molecular mechanisms responsible for MSC-Exos-dependent modulation of tumor progression and discuss insights regarding the therapeutic potential of MSC-Exos in the treatment of malignant diseases.
基金supported by grants from the Serbian Ministry for Education, Science and Technology Development (Grant No.III41026 and 175053)
文摘Objective: Despite recent advancements in targeted therapy and immunotherapies, prognosis for metastatic melanoma patients remains extremely poor. Development of resistance to previously effective treatments presents a serious challenge and new approaches for melanoma treatment are urgently needed. The objective of this study was to examine the effects of telmisartan, an AGTR1 inhibitor and a partial agonist of PPARγ, on melanoma cells as a potential agent for repurposing in melanoma treatment.Methods: Expression of AGTR1 and PPARγ m RNA in melanoma patient tumor samples was examined in publicly available datasets and confirmed in melanoma cell lines by qRT-PCR. A panel of melanoma cell lines was tested in viability, apoptosis and metabolic assays in presence of telmisartan by flow cytometry and immunocytochemistry. A cytotoxic effect of combinations of telmisartan and targeted therapy vemurafenib was examined using the Chou-Talalay combination index method.Results: Both AGTR1 and PPARγ mRNA were expressed in melanoma patient tumor samples and decreased compared to the expression in the healthy skin. In vitro, we found that telmisartan decreased melanoma cell viability by inducing cell apoptosis.Increased glucose uptake, but not utilization, in the presence of telmisartan caused the fission of mitochondria and release of reactive oxygen species. Telmisartan altered the cell bioenergetics, thereby synergizing with vemurafenib in vitro, and even sensitized vemurafenib-resistant cells to the treatment.Conclusions: Given that the effective doses of telmisartan examined in our study can be administered to patients and that telmisartan is a widely used and safe antihypertensive drug, our findings provide the scientific rationale for testing its efficacy in treatment of melanoma progression.
文摘Acute liver failure(ALF)is a severe and life-threatening condition in which rapid deterioration of liver function develops in a patient who has no preexisting liver disease.Mesenchymal stem cells(MSCs)are immunoregulatory stem cells which are able to modulate phenotype and function of all immune cells that play pathogenic role in the development and progression of ALF.MSCs in juxtacrine and paracrine manner attenuate antigen-presenting properties of dendritic cells and macrophages,reduce production of inflammatory cytokines in T lymphocytes,suppress hepatotoxicity of natural killer T(NKT)cells and promote generation and expansion of immunosuppressive T,B and NKT regulatory cells in acutely inflamed liver.Due to their nano-sized dimension and lipid envelope,intravenously injected MSC-derived exosomes(MSC-Exos)may by-pass all biological barriers to deliver MSC-sourced immunoregulatoy factors directly into the liver-infiltrated immune cells and injured hepatocytes.Results obtained by us and others revealed that intravenous administration of MSCs and MSC-Exos efficiently attenuated detrimental immune response and acute inflammation in the liver,suggesting that MSCs and MSC-Exos could be considered as potentially new remedies in the immunotherapy of ALF.In this review,we emphasize the current knowledge about molecular and cellular mechanisms which are responsible for MSC-based modulation of liver-infiltrated immune cells and we discuss different insights regarding the therapeutic potential of MSCs in liver regeneration.
文摘BACKGROUND Rectal cancer(RC)is one of the most common diagnosed cancers,and one of the major causes of cancer-related death nowadays.Majority of the current guidelines rely on TNM classification regarding therapy regiments,however recent studies suggest that additional histopathological findings could affect the disease course.AIM To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival(OS)of RC patients.METHODS A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic,Clinical Center of Serbia,between the years of 2014–2016.All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification.In addition,the patient’s demographics,surgical details,postoperative pathological details,differentiation degree and their correlation with OS was investigated.RESULTS Of 245 included patients with stage Ⅰ-Ⅲ RC,lymphovascular invasion(LVI)was identified in 92 patients(38%),whereas perineural invasion(PNI)was present in 46 patients(19%).Using Kaplan-Meier analysis for overall survival rate,we have found that both LVI and PNI were associated with lower survival rates(P<0.01).Moreover when Cox multiple regression model was used,LVI,PNI,older age,male gender were predictors of poor prognosis(HR=5.49;95%CI:2.889-10.429;P<0.05).CONCLUSION LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients,hence more aggressive therapy should be reserved for these patients after curative resection.
文摘Compliant mechanisms transfer an input force or displacement to another point through elastic body deformation. The field of compliant mechanisms is expected to continue to grow as materials with superior properties are developed. The paper takes into consideration some typical spring guiding systems, being able to realize translating planar displacement of the link. Some types of compound spring guiding systems, such as S-shaped guiding spring system, U-shaped guiding spring system and four spring guiding system with additional rigid-body link have been considered and analyzed as compliant structures. The mobility as well as guiding accuracy of the developed compliant mechanisms, that is, their capability to realize translating planar displacement of the link, have been researched, and the optimal dimensions of the mechanism have been determined in order to provide minimal guiding inaccuracy.
文摘Celiac disease(CD) is a common and well defined autoimmune disorder caused by gliadin and related proteins of wheat,rye,and barley.Epidemiologic studies confirmed that CD is highly associated with other autoimmune diseases and with Down syndrome(DS).The symptomatic form of CD in patients with DSis more frequent than asymptomatic forms.However,growth impairment,anemia,intermittent diarrhea,and constipation are symptoms and signs typically of children with DS without CD.Late identification of the disease can lead to various complications,sometimes even very severe.Therefore,systematic screening for CD is essential in the management of children and adolescents with DS.Many medical organizations recommend screening in this group of patients.However,current policy statements vary in their recommendations for screening and there is still a need for establishing uniform diagnostic criteria.
文摘Energy sector represents a key industrial branch for national, environmental and economic success. With its exclusive access to domestic deposits, lignite industry represents a guarantor of reliable raw materials, offering long-term supply security based on verified reserves. Currently operated coalmines in Serbia (Kolubara and Kostolac) have production around 36 million tons of lignite, and over 108 million m3 of overburden. Consequently, sustainability of lignite production requires cost reduction and environmental protection, as well as capacity increase. In order to rationalise, and increase efficiency of Serbian lignite mines, it is necessary to focus the activities on major issues shown within the triangle of energy policy objectives (security of supply, competi- tive prices and environmental protection). Production process optimisation singled out several special programs. Equipment revi- talization and modernization is necessary taking into account that majority of the currently operated machinery has a life up to 25 years. Production process automation would enable high level of technical operation in the field of open cast mines management. Lack of coal quality uniformity is the permanent problem resulting by great amounts of coal reserves to be used uneconomically. Planning and training at all levels and finally cooperative software for business procedures and work order management. The measures suggested are a key precondition for maintaining competitive position of lignite production on international level.
文摘AIMTo establish the role of nitric oxide (NO), ascorbic acid and tumour necrosis factor-α (TNF-α) in the pathogenesis of pseudoexfoliation glaucoma (XFG).METHODSOur study included 120 patients who were referred for cataract surgery. All patients were divided into four groups according to clinical findings: XFG, early and late pseudoexfoliation syndrome (XFS), and cataract (without pseudoexfoliation). Serum and aqueous humour levels of the ascorbic acid, NO and TNF-α were measured. The concentrations of the ascorbic acid and NO were measured by an appropriate spectrophotometric method. Enzyme-linked immunosorbent assay (ELISA) was used to determine TNF-α level.RESULTSAqueous humour concentration of ascorbic acid was significantly lower in patients with late XFS (0.61±0.11 mmol/L) and XFG (0.48±0.15 mmol/L) compared to patients with early XFS (0.9±0.15 mmol/L) and cataract (1.16±0.22 mmol/L), while there was no difference in serum concentration in all examined groups. Aqueous humour concentration of NO was significantly higher in patients with XFG (77.7±11.4 µmol/L) compared to patients with early XFS (50.27±9.34 µmol/L) and cataract (49.77±7.1 µmol/L), while serum concentration was increased in the early stage of XFS (73.26±8.29 µmol/L). Aqueous humour level of proinflammatory cytokine TNF-α was increased in patients with XFS (early 460.04±18.32 pg/mL; late 502.42±53.23 pg/mL) and XFG (510.34±43.07 pg/mL), while there was no difference in serum level in all examined groups of patients.CONCLUSIONReduced ascorbic acid and elevated NO and inflammation related cytokine TNF-α level in aqueous humour of the patients with developed XFG suggest that oxidative stress induces local inflammation.
基金Supported by Ministry of Science of Serbia,Project No.145061
文摘AIM： To evaluate the clinical characteristics of splenic marginal-zone lymphoma （SMZL） following antigen expression and the influence of therapeutic approaches on clinical outcome and overall survival （OS）.METHODS： A total of 30 patients with typical histological and immunohistochemical SMZL patterns were examined. Splenectomy plus chemotherapy was applied in 20 patients, while splenectomy as a single treatment-option was performed in 10 patients. Prognostic factor and overall survival rate were analyzed.RESULTS： Complete remission （CR） was achieved in 20 （66.7%）, partial remission （PR） in seven （23.3%）, and lethal outcome due to disease progression occurred in three （10.0%） patients. Median survival of patients with a splenectomy was 93.0 mo and for patients with splenectomy plus chemotherapy it was 207.5 mo （Log rank = 0.056, P 〉 0.05）. Time from onset of first symptoms to the beginning of the treatment （mean 9.4 too） was influenced by spleen dimensions, as measured by computerized tomography and ultra-sound （t = 2.558, P = 0.018）. Strong positivity （＋＋＋） of CD20 antigen expression in splenic tissue had a positive influence on OS （Log rank = 5.244, P 〈 0.05）. The analysis of factors interfering with survival （by the Kaplan-Meier method） revealed that gender, general symptoms, clinical stage, and spleen infiltration type （nodular vs diffuse） had no significant （P 〉 0.05） effects on the OS. The expression of other antigens （immunohistochemistry） also had no effect on survival-rate, as measured by a χ^2 test （P 〉 0.05）.CONCLUSION： Initial splenectomy combined with chemotherapy has been shown to be beneficial due to its advanced remission rate/duration; however, a larger controlled clinical study is required to confirm our findings.
文摘Background:We examined the associations of cardiorespiratory fitness(CRF) and white blood cell count(WBC) with mortality outcomes.Methods: A total of 52,056 apparently healthy adults completed a comprehensive health examination,including a maximal treadmill test and blood chemistry analyses.CRF was categorized as high,moderate,or low by age and sex;WBC was categorized as sex-specific quartiles.Results:During 17.8± 9.5 years(mean± SD) of follow-up,a total of 4088 deaths occurred.When regressed jointly,significantly decreased allcause mortality across CRF categories was observed within each quartile of WBC in men.Within WBC Quartile 1,all-cause mortality hazard ratios(HRs) with a 95% confidence interval(95%CI) were 1.0(referent),1.29(95%CI:1.06-1.57),and 2.03(95%CI:1.42-2.92) for high,moderate,and low CRF categories,respectively(p for trend <0.001).Similar trends were observed in the remaining 3 quartiles.With the exception of cardiovascular disease(CVD) mortality within Quartile 1(p for trend=0.743),there were also similar trends across CRF categories within WBC quartiles in men for both CVD and cancer mortality(p for trend <0.01 for all).For women,there were no significant trends across CRF categories for mortality outcomes within Quartiles 1-3.However,we observed significantly decreased all-cause mortality across CRF categories within WBC Quartile 4(HR=1.05(95%CI:0.76-1.44),HR=1.63(95%CI:1.20-2.21),and HR=1.87(95%CI:1.29-2.69) for high,moderate,and low CRF,respectively(p for trend=0.002)).Similar trends in women were observed for CVD and cancer mortality within WBC Quartile 4 only.Conclusion:There are strong joint associations between CRF,WBC,and all-cause,CVD,and cancer mortality in men;these associations are less consistent in women.
文摘Charles Darwin was deeply interested in carnivorous plants and was particularly fascinated by Venus flytrap(Dionaea muscipula)and sundew plants(Drosera spp.)of the Droseraceae family.He was intrigued by fast and slow trap movements in these plants and predicted the existence of a signal that transfers information from sensor to actuator within the trap organ.Based on his request,Sir John Burdon-Sanderson discovered electrical signals in Venus flytrap.Recent success in the transformation of non-model carnivorous plants with a Ca2+sensor has outlined a possible route for the evolution of sensory systems in the carnivorous family Droseraceae.
基金Ministry of Science,Education and Technology Republic of Serbia,No. 175018。
文摘BACKGROUND Neuroendocrine tumors of appendix(ANETs)known as carcinoids,are rare endocrine neoplasms originated from enterochromaffin cells of gastrointestinal tract.ANETs are the third most frequent(16.7%)gastrointestinal neuroendocrine tumors,with the incidence of 0.08-0.2 cases/100000 during one year.Incidental ANETs occur in 0.2%-0.7%of emergency surgical resections because of suspected appendicitis which is usually the first manifestation of ANET.Although there are a lot of papers about application of somatostatin receptor scintigraphy in gastrointestinal neuroendocrine tumors,there are very rare sporadic cases described about ANETs particularly.AIM To establish the role of somatostatin receptor scintigraphy(SRS)in the management of patients with neuroendocrine tumors of appendix(ANET).METHODS The total of 35 patients was investigated,23 females and 12 males,average age(43.7±17.3 years).All patients had histological diagnosis of ANET(34 carcinoids of appendix and one tubular carcinoid).Majority of tumors have been found incidentally during surgery of:Acute appendicitis(n=15),perforated appendicitis(n=2),ileus(n=3),hysterectomy(n=3),ruptured ovarian cyst(n=2),caecal volvulus(n=1),while 9 patients had diagnosis of appendiceal tumor before the surgery.Seventeen patients had tumor grade(G)G1,12 G2 and 6 G3.The right hemicolectomy was performed in 13,while the rest of the patients had appendectomy only.SRS was done early(2 h)and late(24 h)after i.v.application of 740 MBq technetium-99 m ethylenediamine-N,N’-diacetic acid Hydrazinonicotinyl-Tyr3-Octreotide(technetium-99 m-Tektrotyd,Polatom,Poland).SRS was performed for restaging in all the patients after surgery.RESULTS There were 12 true positive(TP),19 true negative,3 false positive and 1 false negative SRS result.Sensitivity of the method was 92.31%,specificity was 86.36%,positive predictive value was 80.00%,negative predictive value was 95.00%and accuracy 88.57%.Receiver operating characteristics analysis showed that SRS scintigraphy is a good test for detec
基金This work was supported by European Crohn’s and Colitis Organization(ECCO)(Grant“The role of galectin 3 in acute colitis”),Serbian Ministry of Science(Grant Nos.ON175069 and ON175103)Faculty of Medical Sciences University of Kragujevac(Grant No.MP01/18).
文摘Detrimental immune response has a crucially important role in the development and progression of inflammatory eye diseases.Inflammatory mediators and proteolytic enzymes released by activated immune cells induce serious injury of corneal epithelial cells and retinal ganglion cell which may result in the vision loss.Mesenchymal stem cells(MSCs)are regulatory cells which produce various immunosuppressive factors that modulate phenotype and function of inflammatory immune cells.However,several safety issues,including undesired differentiation and emboli formation,limit clinical use of MSCs.MSC-derived exosomes(MSC-Exos)are nano-sized extracellular vesicles which contain all MSC-derived immunoregulatory factors.Intraocular administration of MSCExos efficiently attenuated eye inflammation and significantly improved visual acuity in experimental animals without causing any severe side effects.As cell-free product,MSC-Exos addressed all safety issues related to the transplantation of MSCs.Therefore,MSC-Exos could be considered as potentially new remedy for the treatment of inflammatory eye diseases which efficacy should be explored in up-coming clinical trials.
文摘Planning and production optimization within multiple mines or several work sites （entities） mining systems by using fuzzy linear programming （LP） was studied. LP is the most commonly used operations research methods in mining engineering. After the introductory review of properties and limitations of applying LP, short reviews of the general settings of deterministic and fuzzy LP models are presented. With the purpose of comparative analysis, the application of both LP models is presented using the example of the Bauxite Basin Niksic with five mines. After the assessment, LP is an efficient mathematical modeling tool in production planning and solving many other single-criteria optimization problems of mining engineering. After the comparison of advantages and deficiencies of both deterministic and fuzzy LP models, the conclusion presents benefits of the fuzzy LP model but is also stating that seeking the optimal plan of production means to accomplish the overall analysis that will encompass the LP model approaches.
