Assessment of Mercury in Diagnostic Biomaterials of Different Population Groups in Urban Areas of the Moscow Region

The results of a survey of different population groups in urban areas of the Moscow Region (industry workers, residents of areas with increased anthropogenic load of mercury and conditionally pristine areas, cohorts of pregnant women and children) to assess the contents of mercury in samples of various diagnostic biomaterials taken during the course of research are presented. Mercury concentrations in venous and umbilical cord blood, urine, hair, and nails were determined by means of instrumental neutron activation analysis and cold vapor atomic absorption spectrometry. Peculiarities of selection, transportation, storage, and preparation for analysis of samples of hair, nails, urine and umbilical venous blood are described. The determined concentrations of mercury in the studied diagnostic biomaterials are compared with normal and thresholds values. Although increased mercury concentrations were observed in some cases, no significant exposure of mercury was evident in general in the study towns. A positive correlation between the degree of consumption of seafood during pregnancy and a high content of mercury in the analyzed diagnostic biomaterials was shown.

Revealing True and False Brain States Based on Wavelet Analysis of Electroencephalogram

Statement of the Problem: As you know, there exist two different states in the brain’s mental activity: true and false. In recent years, a progressive method of wavelet transformation of the electroencephalogram (EEG) has been developed, which enabled us to establish the fundamental possibility of direct objective registration of the human brain’s mental activity. Earlier, we created an experimental model and software for recognizing true and false mental responses of a person based on the EEG wavelet transformation and described it in the article. The developed experimental model and information software made it possible to compare the two mental states of brain activity by electroencephalographic indicators, one of which is false and the other is true. The goal is to develop a fundamentally new information technology for recognizing true and false states in the brain’s mental activity based on the wavelet transformation of the electroencephalogram. Results: It was revealed that the true and false states of the brain can be distinguished using the method of continuous wavelet transformation and calculation of the EEG wavelet energy. It is shown that the main differences between true and false mental responses are observed in the delta and alpha ranges of the EEG. In the EEG delta rhythm, the wavelet energy is reliably higher in case of a false answer compared to a true one. In the EEG alpha rhythm, the wavelet energy is significantly higher with a true answer than a false one. Practical significance of the research: The data obtained open up the fundamental possibility of identifying true and false mental states of the brain on the basis of continuous wavelet transformation and calculation of the EEG wavelet energy.

Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

Autophagy is a cellular catabolic process characterized by the formation of double-membrane autophagosomes.Transmission electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation.A large number of studies have shown that autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal(GI)cells.However,the role of autophagy in GI diseases remains controversial.This article focuses on the morphological and biochemical characteristics of autophagy in GI diseases,in order to provide new ideas for their diagnosis and treatment.

Corrigendum to“Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review”[J.Pharm.Anal.14(2024)100919]

Original statement in the Section 2:2.Literature search Our primary screening of 180 articles yielded the relevant data for this study.2.1.Study selection A total of 180 articles spanning from 1960 to the present day,including original research,reviews,case reports and studies reporting nitrosamine impurities above the no-observed-adverse-effect levels(NOAEL)established by regulatory agencies,were initially screened.During the primary screening,we considered factors such as relevance,publication date,access to the full article text,and content.

Comparison of da Vinci 5 with previous versions of da Vinci and Sina:A review

Robotic systems have become popular in modern surgical procedures.The option of telesurgery has effectively addressed geographic limitations.These systems are offered by numerous companies worldwide.In this review article,we discuss four models of robotic systems to determine their advantages:the Sina flex system from Iran and the da Vinci Xi,SP,and 5 systems from the USA.We compared aspects such as architecture,instruments,visualizations,clinical use,and costs.Our findings suggest that the da Vinci robot,which was introduced earlier than the Sina system,utilizes proprietary and limited-use EndoWrist instruments with diameters ranging from 8 to 12 mm and features advanced imaging capabilities,including three-dimensional optical,tomographic,and fluorescence imaging.It is well established and widely utilized in various surgical procedures.Conversely,the Sina flex system employs single-use 5 mm instruments and is equipped with two-dimensional optical imaging as a standard,with optional three-dimensional and fluorescence imaging upgrades available.Despite its affordability,the Sina flex system is relatively new and has not yet been clinically tested.Additionally,the Sina flex system is more user-friendly.

Changes in renal function and morphological variations of kidney diseases in rheumatoid arthritis patients

Objective:Rheumatoid nephropathy is one of the most severe extra-articular manifestations of rheumatoid arthritis(RA)associated with a very unfavorable prognosis.This study aimed to identify changes in renal function and morphological variations of kidney diseases in RA patients.Methods:The study enrolled patients(126 patients)between 18 and 55 years of age with a confirmed active RA of more than 12 months.Each patient underwent the following range of laboratory and instrumental research methods:general clinical analysis of blood and urine,performing urinalysis according to Nechiporenko method;determining daily proteinuria;determining the blood content of glucose,urea,creatinine,uric acid,total bilirubin,liver transaminase level,ionogram,lipidogram,and coagulogram;determining the blood content of rheumatoid factor,anti-streptolysin O,and C-reactive protein;and X-ray of the joints of hands and feet.Renal function was examined by estimating glomerular filtration rate,tubular reabsorption index,and renal functional reserve.For studying the morphological changes in the kidneys under ultrasound examination,renal biopsy was performed in 31 patients with RA with urinary syndrome(proteinuria more than 0.3 g per day and hematuria).Results:Nephropathy in RA is characterized by impaired renal function and manifested by an increased blood creatinine and a decrease in glomerular filtration rate and renal functional reserve.Among morphological variations of nephropathy at RA,mesangial proliferative glomerulonephritis prevails,accounting for 48.4%of patients.Other disorders include the secondary amyloidosis(29.0%of patients),tubulointerstitial nephritis(16.1%),membranous glomerulonephritis(3.2%),and focal-segmental glomerulosclerosis(3.2%).Conclusion:Kidney damage is a common systemic manifestation of RA with a long and active course,a major nephropathy trigger.

Nitrosamines crisis in pharmaceuticals-Insights on toxicological implications,root causes and risk assessment:A systematic review

The presence of N-nitroso compounds,particularly N-nitrosamines,in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects.This systematic review investigates their toxicity in active pharmaceutical ingredients(APIs),drug products,and pharmaceutical excipients,along with novel analytical strategies for detection,root cause analysis,reformulation strategies,and regulatory guidelines for nitrosamines.This review emphasizes the molecular toxicity of N-nitroso compounds,focusing on genotoxic,mutagenic,carcinogenic,and other physiological effects.Additionally,it addresses the ongoing nitrosamine crisis,the development of nitrosamine-free products,and the importance of sensitive detection methods and precise risk evaluation.This comprehensive overview will aid molecular biologists,analytical scientists,formulation scientists in research and development sector,and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

Orbital reconstruction:From simple materials to bioengineered solutions

Orbital fractures are a frequent and serious problem for practicing ophthalmologists. The complexity of the pathology is explained by the combined nature of the injuries(often associated with craniofacial injuries), multistage treatments, results that are often unsatisfactory, and a wide range of complaints about functional and cosmetic limitations. Over the years, significant progress has been made in the field of orbital reconstruction,allowing the transition from traditional methods using simple materials to innovative bioengineering solutions.This evolution has been driven by advances in surgical technologies, imaging techniques, and biomaterials aimed at optimizing the restoration of the shape and function of the orbital region. Traditional approaches are based on the use of autologous tissues such as bone grafts and muscle flaps, which provide biocompatibility and natural integration, but have limitations in terms of customization and accessibility. The advent of patient-specific implants and 3D printing technology has revolutionized the reconstruction of the orbit, allowing implants to be precisely adapted to a patient's anatomy. Biocompatible materials, such as porous polyethylene, titanium, and silicone, have become the basis for orbital reconstruction, ensuring durability and compatibility while minimizing long-term complications. Bioengineered solutions hold promise for further advancements in orbital reconstruction. We searched Pub Med, Cyberleninka, and other verified databases for published articles on orbital reconstruction reported in the literature between 1960 and January 2024. In this article, we consider the advantages and disadvantages of each category of reconstruction materials and provide up-to-date information on the methods for modifying their properties using modern processing technologies.

Effectiveness of negative pressure wound therapy in complex surgical treatment of necrotizing fasciitis of the upper limb

BACKGROUND Necrotizing fasciitis(NF)of the upper extremities is a severe surgical pathology,and the incidence of this disease has been steadily increasing in recent decades.Surgical treatment is accompanied by the formation of extensive wounds,which can be treated with significant difficulties.In recent years,negative pressure wound therapy(NPWT)has proven to be highly effective.It is also promising for the treatment of NF.AIM To explore the effectiveness of NPWT in the treatment of NF of the upper extremities.METHODS The results of the treatment of 36 patients with NF of the upper extremities in two groups(NPWT group and control group;2022−2023)were retrospectively analyzed.In the NPWT group,the NPWT method(120 mmHg;constant mode)was used after surgical treatment.The number of vacuum-assisted dressings in patients ranged from 1 to 3,depending on the dynamics of the wound process.The duration of fixation of one bandage was up to 2−3 d.In the control group,conventional methods of local wound treatment were used.The following indicators were analyzed:The treatment delay,the prevalence of inflammation,the microbial landscape,the number of debridements,the duration of wound preparation for surgical closure,and the nature of skin plastic surgery.RESULTS Most patients experienced a significant treatment delay[4 d,interquartile range(IQR):2–7 d],which led to the spread of the pathological process to the forearm and shoulder.The most common pathogens were Staphylococcus aureus(14;38.9%)and Streptococcus pyogenes(22;61.1%).The average number of debridements per patient was 5(IQR:3–7),with no difference between groups.The average time to prepare wounds for surgical closure was 11±4 d in the NPWT group and 29±10 d(P=0.00001)in the control group.In the NPWT group,the wounds were more often closed with local tissues(15;83.3%),and in the control group,split-thickness skin grafts were more often used(4;50%).CONCLUSION The predominant isolation of Staphylococcus aureus and/or Streptococcus pyogenes from the lesions allowed us to classify these patients as NF type II.Multiple debridement procedures have become a feature of this disease treatment.The use of NPWT has significantly reduced the time required to prepare wounds for surgical closure.Early closure of wounds allows for more frequent use of local tissue repair,which ensures better results.NPWT is a highly effective way to prepare wounds for early surgical closure in patients with upper extremity NF.

Characteristics of gut microbiota in anastomotic leakage patients in cold zones post-colorectal cancer surgery: A high-throughput sequencing and propensity-score matching study

Objective:The study aimed to explore the association between gut microbiota and anastomotic leakage(AL)after surgery in colorectal cancer(CRC)patients from a frigid zone,based on high-throughput sequencing.Methods:A total of 98 CRC patients admitted to the Second Affiliated Hospital of Harbin Medical University from July 2018 to February 2019,who met the inclusion criteria,were included.Among these,10 patients were diagnosed as AL.After propensity-score matching of baseline characteristics,10 patients from the anastomotic leakage group(AG)and 10 patients from the normal group(NG)were finally included in this study.Fecal samples were collected,and total DNA was extracted for high-throughput sequencing and bioinformatic analysis.Results:Alpha diversity analysis showed no significant difference between the two groups,while beta diversity analysis revealed significant differences in principal components.Differential microbiota were classified as Proteobacteria at the phylum level(P=0.021).At the genus level,the abundances of Streptococcus(P=0.045),Citrobacter(P=0.008)and Klebsiella(P=0.002)were significantly different between the two groups.LEfSe analysis indicated that these genera contributed most to the differences between the groups.Conclusion:The characteristics of the gut microbiota in the AG and NG were significantly different,and these differences might be associated with AL in CRC patients from frigid zones.

基层医疗机构政府补助受益公平性分析

目的分析政府对基层医疗机构补助的受益公平性。方法利用受益归属分析方法,应用集中指数和Kakwani指数测算居民获得基层医疗机构政府补助的不公平程度。结果 2013年样本地区基层医疗机构政府补助水平显著提高。2008年和2013年基层医疗机构补助的集中指数分别为0.073和-0.120,由倾向于高收入人群变为倾向于低收入人群。2008年和2013年的Kakwani指数分别为-0.303和-0.444,表明政府对基层医疗机构的补助是累退的。结论新医改以后基层医疗机构政府补助水平显著提高,政府基层医疗补助的绝对公平性和相对公平性均有所提高。

Antibiotics,gut microbiota,and irritable bowel syndrome:What are the relations?

Irritable bowel syndrome(IBS)is a functional gastrointestinal disorder in which recurrent abdominal pain is associated with defecation or a change in bowel habits(constipation,diarrhea,or both),and it is often accompanied by symptoms of abdominal bloating and distension.IBS is an important health care issue because it negatively affects the quality of life of patients and places a considerable financial burden on health care systems.Despite extensive research,the etiology and underlying pathophysiology of IBS remain incompletely understood.Proposed mechanisms involved in its pathogenesis include increased intestinal permeability,changes in the immune system,visceral hypersensitivity,impaired gut motility,and emotional disorders.Recently,accumulating evidence has highlighted the important role of the gut microbiota in the development of IBS.Microbial dysbiosis within the gut is thought to contribute to all aspects of its multifactorial pathogenesis.The last few decades have also seen an increasing interest in the impact of antibiotics on the gut microbiota.Moreover,antibiotics have been suggested to play a role in the development of IBS.Extensive research has established that antibacterial therapy induces remarkable shifts in the bacterial community composition that are quite similar to those observed in IBS.This suggestion is further supported by data from cohort and case-control studies,indicating that antibiotic treatment is associated with an increased risk of IBS.This paper summarizes the main findings on this issue and contributes to a deeper understanding of the link between antibiotic use and the development of IBS.

Essential oils and functional herbs for healthy aging

As total life expectancy increases, the prevalence of age-related diseases such as diabetes and Alzheimer's disease is also increasing. Many hypotheses about Alzheimer's disease have been developed, including cholinergic neuron damage, oxidative stress, and inflammation. Acetylcholine is a major neurotransmitter in the brain and cholinergic deficits leads to cognitive dysfunction and decline. Recent studies have linked diabetes as a risk factor in developing Alzheimer's disease and other types of dementia. The incidence of patients with type II diabetes and increased levels and activity of α-amylase is higher in patients with dementia. It has been shown that aromatherapy with essential oils from the mint family can improve cognitive performance in Alzheimer's disease patients. Selected monoterpenoids from these essential oils are reported to inhibit acetylcholinesterase, both in vitro and in vivo. Terpenoids are small, fat-soluble organic molecules that can transfer across nasal mucosa if inhaled, or penetrate through the skin after topical application, enter into the blood and cross the blood-brain barrier. Recent evidence supports the idea that the common constituents of essential oils also inhibit α-amylase, a starch digestive enzyme that plays an important role in the control of diabetes. The mint family is a fragrant plant family that contains most of the culinary herbs found in the Mediterranean diet. The Mediterranean diet is considered to be one of the healthiest diets in the world, and is found to be beneficial not only for the heart but also for the brain. Herbs used in this diet are rich in antioxidants that can prevent oxidative damage caused by free radicals. However, our study shows that they also contain biologically active compounds with potent α-amylase and acetylcholinesterase inhibitory activities. Consumption of fresh herbs can help boost memory and reduce sugar levels in the body. The use of herbs as a functional food could lead to significant improvements in health. Cognitive stimulation with medical food and medical herbs could delay development of cognitive decline, and improve the quality of life of Alzheimer's disease patients. This effect can be enhanced if combined with aromatherapy, topically or by inhalation, and/or by ingestion. Terpenes and terpenoids, the primary constituents of these essential oils are small, lipid soluble organic molecules that can be absorbed through the skin or across nasal mucosa into the systemic blood circulation. Many terpenes can also cross the blood-brain barrier. Therefore, topical application or inhalation of essential oils will also produce a systemic effect.

Daclatasvir plus asunaprevir in treatment-na?ve patients with hepatitis C virus genotype 1b infection

AIM To assess daclatasvir plus asunaprevir(d UAL) in treatment-na?ve patients from China's Mainland, Russia and South Korea with hepatitis C virus(HCV) genotype 1 b infection. METHODS Patients were randomly assigned(3:1) to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period(immediate treatment arm) or following 12 wk of matching placebo(placebodeferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin(70%) among patients in the immediate treatment arm. The first 12 wk of the study were blinded. Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase), and during 24 wk of d UAL in both arms combined.RESULTS In total, 207 patients were randomly assigned to immediate(n = 155) or placebo-deferred(n = 52) treatment. Most patients were Asian(86%), female(59%) and aged < 65 years(90%). Among them, 13% had cirrhosis, 32% had IL28 B non-CC genotypes and 53% had baseline HCV RNA levels of ≥ 6 million IU/m L. Among patients in the immediate treatment arm, SVR12 was achieved by 92%(95% confidence interval: 87.2-96.0), which was significantly higher than the historical comparator rate(70%). SVR12 was largely unaffected by cirrhosis(89%), age ≥ 65 years(92%), male sex(90%), baseline HCV RNA ≥ 6 million(89%) or IL28 B non-CC genotypes(96%), although SVR12 was higher among patients without(96%) than among those with(53%) baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H). during the double-blind phase, aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL. during 24 wk of d UAL therapy(combined arms), the most common adverse events(≥ 10%) were elevated alanine aminotransferase and upper respiratory tract infection; emergent grade 3-4 laboratory abnormalities were infrequently observed, and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase, n = 9; aspartate transaminase, n = 6) reversed within 8-11 d. Two patients discontinued d UAL treatment; one due to aminotransferase elevations, nausea, and jaundice and the other due to a fatal adverse event unrelated to treatment. There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study, and SVR12 with d UAL treatment(92%) exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.

Molecular pathways of liver regeneration:A comprehensive review

The liver is a unique parenchymal organ with a regenerative capacity allowing it to restore up to 70%of its volume.Although knowledge of this phenomenon dates back to Greek mythology(the story of Prometheus),many aspects of liver regeneration are still not understood.A variety of different factors,including inflammatory cytokines,growth factors,and bile acids,promote liver regeneration and control the final size of the organ during typical regeneration,which is performed by mature hepatocytes,and during alternative regeneration,which is performed by recently identified resident stem cells called“hepatic progenitor cells”.Hepatic progenitor cells drive liver regeneration when hepatocytes are unable to restore the liver mass,such as in cases of chronic injury or excessive acute injury.In liver maintenance,the body mass ratio is essential for homeostasis because the liver has numerous functions;therefore,a greater understanding of this process will lead to better control of liver injuries,improved transplantation of small grafts and the discovery of new methods for the treatment of liver diseases.The current review sheds light on the key molecular pathways and cells involved in typical and progenitor-dependent liver mass regeneration after various acute or chronic injuries.Subsequent studies and a better understanding of liver regeneration will lead to the development of new therapeutic methods for liver diseases.

Risk modeling of femoral neck fracture based on geometric parameters of the proximal epiphysis

BACKGROUND Fractures of the proximal femur epiphysis are problematic for state health care because they are associated with severe medical and social problems and high morbidity and mortality rates.AIM To model the potential risk of hip fracture via femur geometric parameters.METHODS Seventy educational cadaveric femurs from people aged 14 to 80 years,10 X-ray images from the records of the Human Anatomy Department and 10 X-ray images from the Department of Traumatology,Orthopedics and Disaster Surgery of Sechenov University,were evaluated.The parameters of the fractured bone were measured using images captured with a Canon d60 camera.The projection values of the proximal epiphysis of the cadaveric femurs and geometric parameters of the bones shown in the X-ray images were measured with Autodesk software(AutoCAD 2018).Analysis of the video frames showing bone rotation reveal that the greater trochanter can be inscribed in a parallelepiped,where one of the faces is parallel to the plane of view in the frontal standard projection and is rectangular.The angle of bone rotation obtained by turning the cube corresponded to the angle measured with the second technique.This reliable method of calculating the rotation of the bone relative to the anterior projection was employed in subsequent calculations.The geometric parameters of the femur were measured using X-ray images according to the proposed method.RESULTS The geometric parameters of 70 femurs were analyzed,and correlation coefficients were calculated.Our measurement results were compared with those reported by other authors.The potential influence of femur geometry on force distribution in the proximal epiphysis of the femur was described,and a 2-dimensional model of the femur epiphysis associated with minimal neck fracture risk was provided.The assessment of the geometric parameters of the femoral epiphysis indicated the greatest risk of a varus fracture of the neck if the angle of the minimal resistance zone(AMRZ)index>24°and the neck-shaft angle(NSA)<127.5°.In contrast,the minimum risk was observed at AMRZ<14°and NSA>128.87°.CONCLUSION The proposed method provides the potential femur neck fracture risk based on geometric parameters.

Clostridioides difficile infection in patients with nonalcoholic fatty liver disease-current status

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,leading to fibrosis,cirrhosis and hepatocellular carcinoma and also associated with increased cardiovascular disease mortality.The pathogenesis of NAFLD is not fully understood,although NAFLD is thought to be a hepatic form of metabolic syndrome.There is an increasing understanding of the role of microbiota disturbances in NAFLD pathogenesis,and as with many other conditions affecting the microbiota,NAFLD may be a novel risk factor for Clostridioides difficile(C.difficile)colonization(CDC)and C.difficile infection(CDI).CDI is an emerging nosocomial disease,and community-acquired cases of infection are growing,probably due to an increase in CDC rates.The association of NAFLD with CDI has been shown in only 4 studies to date,three of which included less than 1000 patients,although the frequency of NAFLD in these studies was observed in almost 20%of the total patient cohort.These data revealed that NAFLD is a risk factor for CDI development and,moreover,is a risk factor for intestinal complications of CDI.More studies are needed to investigate this association and move forward CDC and CDI screening efforts for this group of patients.

Primary lymphomas of the genitourinary tract:A population-based study

Objective:We performed a population-based analysis focusing on primary extranodal lymphoma of either testis,kidney,bladder or prostate(PGUL).Methods:We identified all cases of localized testis,renal,bladder and prostate primary lymphomas(PL)versus primary testis,kidney,bladder and prostate cancers within the Surveillance,Epidemiology,and End Results database(1998e2015).Estimated annual proportion change methodology(EAPC),multivariable logistic regression models,cumulative incidence plots and multivariable competing risks regression models were used.Results:The rates of testis-PL,renal-PL,bladder-PL and prostate-PL were 3.04%,0.22%,0.18%and 0.01%,respectively.Patients with PGUL were older and more frequently Caucasian.Annual rates significantly decreased for renal-PL(EAPC:5.6%;pZ0.004)and prostate-PL(EAPC:3.6%;pZ0.03).In multivariable logistic regression models,older ager independently predicted testis-PL(odds ratio[OR]:16.4;p<0.001)and renal-PL(OR:3.5;p<0.001),while female gender independently predicted bladder-PL(OR:5.5;p<0.001).In surgically treated patients,cumulative incidence plots showed significantly higher 10-year cancer-specific mortality(CSM)rates for testis-PL,renal-PL and prostate-PL versus their primary genitourinary tumors.In multivariable competing risks regression models,only testis-PL(hazard ratio[HR]:16.7;p<0.001)and renal-PL(HR:2.52;p<0.001)independently predicted higher CSM rates.Conclusion:PGUL rates are extremely low and on the decrease in kidney and prostate but stable in testis and bladder.Relative to primary genitourinary tumors,PGUL are associated with worse CSM for testis-PL and renal-PL but not for bladder-PL and prostate-PL,even after adjustment for other-cause mortality.

To Knowledge of the Origin of the Brain Mental Activity

This paper is devoted towards the origin of a human subjective state, and we present a methodology for studying the origin of brain activity. We were first to reveal that the subjective states of a human being can be subjected to an objective remote registration. Recently we have established the existence of the so-called “psychogenic field”, which reflects the subjective state of human brain. The subjective state of a human being was shown to affect remotely the physicochemical properties of the blood. The interaction of neurophysiological and subjective processes is described in the context of systemic organization of a goal-directed behavior. An original schematic diagram is presented to describe the formation of a subjective brain state. This approach is based on the feedback influence of a psychogenic field on neuronal molecular processes (self-induction in the brain). We propose a paradigm for the origin of a subjective state and possible existence of physical phenomena and brain fields, which are unique for the active brain.