Personalized treatment of malignant tumors during pregnancy.

The combination of pregnancy and cancer is a challenge for the patient and a problematic clinical dilemma for the doctor. In this retrospective observational cohort study, we have tried to analyze our experience in the management of such patients. This review includes 41 patients with malignant neoplasms detected during pregnancy who received treatment at the Almazov National Medical Research Centre from 2015-2021. The majority of patients received treatment during pregnancy (n=26, 63.4%): chemotherapy - 19 (46.3%) (in 2 cases in combination with surgery), surgical treatment - 7 (17, 1%) patients. In most cases, delivery was at term (n=28, 68.3%). All children born at term were mature and had no growth restriction, regardless of whether the mothers received treatment during pregnancy or not. When detecting cancer during pregnancy, an immediate follow-up examination is required to assess the extent of the tumor and current fetal state. If pregnancy prolongation is requested, the treatment should not be postponed, except for systemic chemotherapy in the first trimester of pregnancy, pelvic radiation at any term.

The ins and outs of male breast and anterior chest wall lesions from childhood to adulthood.

Physiological and pathological processes arising from the breast and anterior chest wall may share similar clinical presentations because of the small volume of male breasts. Therefore, imaging is frequently required to localise and characterise the lesion and guide biopsy when radiological findings are equivocal or suspicious. Mammography or digital breast tomosynthesis (DBT) and ultrasound are the mainstays of breast imaging work-up. Other imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography (PET) can sometimes augment the investigation and aid treatment planning. This article reviews the key imaging features of a wide spectrum of benign and malignant conditions that involve the male breast and anterior chest wall across various age groups. Familiarisation with the salient radiological findings is essential for reaching an accurate diagnosis and optimising management.

Association of Common Genetic Risk Variants With Gestational Diabetes Mellitus and Their Role in GDM Prediction.

Objective: We aimed to explore the associations between common genetic risk variants with gestational diabetes mellitus (GDM) risk in Russian women and to assess their utility in the identification of GDM cases. Methods: We conducted a case-control study including 1,142 pregnant women (688 GDM cases and 454 controls) enrolled at Almazov National Medical Research Centre. The International Association of Diabetes and Pregnancy Study Groups criteria were used to diagnose GDM. A total of 11 single- nucleotide polymorphisms (SNPs), including those in HKDC1 (rs10762264), GCK (rs1799884), MTNR1B (rs10830963 and rs1387153), TCF7L2 (rs7903146 and rs12255372), KCNJ11 (rs5219), IGF2BP2 (rs4402960), IRS1 (rs1801278), FTO (rs9939609), and CDKAL1 (rs7754840) were genotyped using Taqman assays. A logistic regression model was used to calculate odds ratios (ORs) and their confidence intervals (CIs). A simple-count genetic risk score (GRS) was calculated using 6 SNPs. The area under the receiver operating characteristic curve (c-statistic) was calculated for the logistic regression model predicting the risk of GDM using clinical covariates, SNPs that had shown a significant association with GDM in our study, GRS, and their combinations. Results: Two variants in MTNR1B (rs1387153 and rs10830963) demonstrated a significant association with an increased risk of GDM. The association remained significant after adjustment for age, pre-gestational BMI, arterial hypertension, GDM in history, impaired glucose tolerance, polycystic ovary syndrome, family history of diabetes, and parity (P = 0.001 and P < 0.001, respectively). After being conditioned by each other, the effect of rs1387153 on GDM predisposition weakened while the effect of rs10830963 remained significant (P = 0.004). The risk of GDM was predicted by clinical variables (c-statistic 0.712, 95 % CI: 0.675 - 0.749), and the accuracy of prediction was modestly improved by adding GRS to the model (0.719, 95 % CI 0.682 - 0.755), and more by adding only rs10830963 (0.729, 95 % CI 0.693 - 0.764). Conclusion: Among 11 SNPs associated with T2D and/or GDM in other populations, we confirmed significant association with GDM for two variants in MTNR1B in Russian women. However, these variants showed limited value in the identification of GDM cases.

[Five year experience in ibrutinib therapy for relapsed and refractory mantle cell lymphoma in real world Russian clinical practice].

BACKGROUND: Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients outcomes, but relapse is inevitable. In phase IIIII clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL. AIM: To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials. MATERIALS AND METHODS: The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 24, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity. RESULTS: From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG2 18%, blastoid variant (or Ki6740% or WBC50109/l) 43%. The median number of previous treatment lines was 2 (111). The ORR was 78.4% (CRR 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p0.001), the median OS 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months. The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity 15%, arrhythmia 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications. CONCLUSION: Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.

Circle RNA FOXP1 promotes cell proliferation in lung cancer by regulating miR-185-5p/Wnt1 signaling pathway.

OBJECTIVE: It is reported that circular RNA plays an important role in various cancers in recent years. However, there is less investigation reported in lung adenocarcinoma (LUAD) about circRNA. This study aims to explore the role and molecular mechanism of circle RNA FOXP1 in LUAD procession. PATIENTS AND METHODS: The levels of circFOXP1 and miR-185-5p in LUAD cell lines and LUAD cancer samples were examined by RT-PCR. The functions of circFOXP1 and miR-185-5p at LUAD cells were detected by cell transfection of the overexpression or repression. The A549 and H1299 cell proliferation were detected by MTT assay and colony formation assay. And the cell apoptosis was detected by TUNEL assay. The expression levels WNT1 were measured by Western blot in A549 and H1299 cells. Furthermore, the luciferase assay detected the direct interaction between circFOXP1 and miR-185-5p or miR-185-5p and WNT1. RESULTS: The circFOXP1 expression was increased in LUAD patients and LUAD cell lines. The downregulation of circFOXP1 significantly repressed LUAD cell proliferation and promoted cell apoptosis. Moreover, the luciferase assay results confirmed that circFOXP1 directly interacted with miR-185-5p. Overexpression of miR-185-5p could reverse the effect of circFOXP1 in LUAD cell. Besides, the luciferase results showed that miR-185-5p directly interacted with WNT1. miR-185-5p overexpression inhibited the WNT1 expression, while circFOXP1 repression decreased the WNT1 level in LUAD cell lines. The downregulating WNT1 could reverse the effects of miR-185-5p inhibition in LUAD cell lines. Furthermore, WNT1 was significantly upregulated in LUAD cancer tissues. In addition, circFOXP1 level was negatively correlated with miR-185-5p expression and positively correlated with WNT1 expression in LUAD cancer tissues. CONCLUSIONS: These data suggested that circFOXP1 promoted cell proliferation and repressed cell apoptosis in LUAD by regulating miR-185-5p/WNT1 signaling pathway. It provides a novel potential therapeutic agent for the treatment of LUAD.

Reduction in inappropriate MRI knee studies after implementation of an appropriateness checklist: Experience at a tertiary care centre.

PURPOSE: To evaluate reduction in inappropriate knee MRI requests following implementation of a mandatory knee MRI appropriateness checklist. METHODS: A retrospective review was performed at a single tertiary care centre. A knee MRI appropriateness checklist was developed based on the ACR Appropriateness Criteria and adherence from referring physicians was mandatory. Reports from 200 consecutive knee MRI studies one year prior to implementation were compared to 200 consecutive knee MRI studies following implementation. The presence of moderate or greater osteoarthritis on MRI reports was used as a marker for inappropriate knee MRIs. Patient demographics, wait times, number of knee MRIs, and number of all MRIs at our centre over a six month period post-intervention and pre-intervention were recorded. Differences between pre-intervention and post-intervention presence of moderate or greater osteoarthritis, patient demographics, wait times, and number of MRIs analyzed. RESULTS: A significant decrease was found in moderate or greater grade osteoarthritis following intervention, decreasing from 36.5% to 20.5% (73 studies versus 41 studies, p = 0.023). Of these, the most profound decrease occurred in studies with severe osteoarthritis, with an 80 % decrease (35 studies versus 7 studies, p < 0.001). Post intervention, 48 % fewer knee MRIs were performed in the same time interval (652 studies pre-intervention versus 336 studies post intervention, p < 0.001). No significant differences were found in the patient demographics. CONCLUSION: Mandatory knee MRI appropriateness checklists are associated with a significant reduction in the number of inappropriate studies performed. Follow up studies will be required to assess long-term impact in a larger population.

α-PD-1 therapy elevates Treg/Th balance and increases tumor cell pSmad3 that are both targeted by α-TGFß antibody to promote durable rejection and immunity in squamous cell carcinomas.

BACKGROUND: Checkpoint blockade immunotherapy has improved metastatic cancer patient survival, but response rates remain low. There is an unmet need to identify mechanisms and tools to circumvent resistance. In human patients, responses to checkpoint blockade therapy correlate with tumor mutation load, and intrinsic resistance associates with pre-treatment signatures of epithelial mesenchymal transition (EMT), immunosuppression, macrophage chemotaxis and TGFß signaling. METHODS: To facilitate studies on mechanisms of squamous cell carcinoma (SCC) evasion of checkpoint blockade immunotherapy, we sought to develop a novel panel of murine syngeneic SCC lines reflecting the heterogeneity of human cancer and its responses to immunotherapy. We characterized six Kras-driven cutaneous SCC lines with a range of mutation loads. Following implantation into syngeneic FVB mice, we examined multiple tumor responses to α-PD-1, α-TGFß or combinatorial therapy, including tumor growth rate and regression, tumor immune cell composition, acquired tumor immunity, and the role of cytotoxic T cells and Tregs in immunotherapy responses. RESULTS: We show that α-PD-1 therapy is ineffective in establishing complete regression (CR) of tumors in all six SCC lines, but causes partial tumor growth inhibition of two lines with the highest mutations loads, CCK168 and CCK169. α-TGFß monotherapy results in 20% CR and 10% CR of established CCK168 and CCK169 tumors respectively, together with acquisition of long-term anti-tumor immunity. α-PD-1 synergizes with α-TGFß, increasing CR rates to 60% (CCK168) and 20% (CCK169). α-PD-1 therapy enhances CD4 + Treg/CD4 + Th ratios and increases tumor cell pSmad3 expression in CCK168 SCCs, whereas α-TGFß antibody administration attenuates these effects. We show that α-TGFß acts in part through suppressing immunosuppressive Tregs induced by α-PD-1, that limit the anti-tumor activity of α-PD-1 monotherapy. Additionally, in vitro and in vivo, α-TGFß acts directly on the tumor cell to attenuate EMT, to activate a program of gene expression that stimulates immuno-surveillance, including up regulation of genes encoding the tumor cell antigen presentation machinery. CONCLUSIONS: We show that α-PD-1 not only initiates a tumor rejection program, but can induce a competing TGFß-driven immuno-suppressive program. We identify new opportunities for α-PD-1/α-TGFß combinatorial treatment of SCCs especially those with a high mutation load, high CD4+ T cell content and pSmad3 signaling. Our data form the basis for clinical trial of α-TGFß/α-PD-1 combination therapy (NCT02947165).

[Low protein diet with essential amino acids ketoanalogues combination can affect serum FGF-23 and Klotho levels in chronic kidney disease 3b-4 stages patients: randomized pilot study].

Protein restriction diet (PRD) with ketoanalagues of essential amino acids (KA) combination can improve of chronic kidney disease (CKD) course while, the precise mechanisms of PRD + KAA action in CKD are not known yet. We have conducted a prospective, randomized, controlled study of PRD and KAA patient's group in compare with PRD without KAA group in regarding to serum Klotho and FGF-23 levels in patients with CKD. MATERIALS AND METHODS: The study included 79 CKD 3b-4 stages patients, non - diabetic etiology, used PRD (0.6 g/kg/day). The patients were randomized in two groups: 42 patients, received PRD + KAA (Group 1) and 37 patients continued the PRD without KAA (Group 2). Serum FGF-23 (Human FGF-23 ELISA kit with antibodies to native FGF-23 molecule, Merk Millipore MILLENZFGF-23-32K), Klotho (Human soluble Klotho with antiKlotho monoclonal antibodies, IBL-Takara 27998-96Well) levels, as well as instrumental examination: bioimpedance analysis [assess of muscle body mass (MBM), fat body mass (FBM), body mass index (BMI) and others]; sphygmography [assess of augmentation (stiffness) indices (AI), central (aortal) blood pressure (CBP) by «Sphygmacor¼ device]; as well as echocardiography [assess of cardiac (valvular) calcification score (CCS) and left ventricular myocardium mass index (LVMMI)], were studded in addition to conventional examination. RESULTS AND DISCUSSION: To the end of 14th month of the study the PRD group reached a body mass index (BMI) decrease (p=0.046), including MBM in men (p=0.027) and woman (p=0.044). In addition, higher FGF-23 (p=0.029), and lower Klotho (p=0.037) serum levels were revealed in the PRD group compared to the PRD+KAA group as well as the increase in AI (p=0.034), CCS (p=0.048), and LVMMI (p=0.023). CONCLUSION: Use of PRD + KAA provides adequate nutrition status and more efficient correction of FGF-23 and Klotho imbalance in CKD progression that may contribute to alleviation of both cardiovascular calcification and cardiac remodeling in CKD. Importantly, a prolonged PRD use without supplementation of KAA may lead to malnutrition signs.

[Serum troponin-I as a marker of fibroblast growth factor-23 (FGF-23) cardiotoxic effect, in patients with chronic kidney disease].

AIM: It has been established that an increased fibroblast growth factor (FGF-23) serum levels significantly contribute to the heart and blood vessels remodeling in patients with chronic kidney disease (CKD). But the precise mechanisms of the FGF-23 cardiac effect are currently being actively studied. At the same time, it is believed that the cardiac effects of FGF-23 may be due to the increasing deficit of Klotho protein as CKD progresses. In parallel with these changes, a number of studies indicate the persistence of the detectable troponins serum levels in CKD patients, even in the absence of clear clinical manifestations of cardiovascular diseases (CVD). The aim of the study was to confirm / exclude the existence of a causal relationship between elevated FGF-23, reduced Klotho and elevated troponin-I (as the most specific troponin in CKD). MATERIALS AND METHODS: The study included 130 CKD stages 1-5D patients without clinically pronounced symptoms of СVD (Coronary artery disease, CCS class 2-4, Chronic heart failure, NYHA 24, myocarditis, pericarditis, arrhythmias), as well as the severe arterial hypertension (BP >160/90 mm Hg), according to the laboratory and instrumental methods of examination. The selected group of patients was studied: serum levels of FGF-23 (Human FGF-23 ELISA kit), Klotho (Human soluble Klotho with antiklotho monoclonal antibodies), troponin-I (high - sensitive assay), and also data from instrumental examination methods: electrocardiography (ECG), echocardiography (left ventricular myocardial mass index (LVMI), cardiac (valvular) calcification score (CCS) using a semi - quantitative point scale), sphygmagraphy (augmentation (stiffness) indices of vessels (AI), pulse wave velocity (PWV), central (aortic) blood pressure (CBP), blood supply of subendocardium (BSE) - using "Shygmacor" device (Australia)). RESULTS AND DISCUSSION: The changes in serum levels of FGF-23, Klotho and troponin-I (Tr-I) depended on the stage of CKD. The following correlations were identified: FGF-23 and: Tr-I (r=0.601; p.

The effect of media reporting of a homicide committed by a patient with schizophrenia on the public stigma and knowledge of psychosis among the general population of Hong Kong.

PURPOSE: This study aimed to investigate the effects of media reporting of a homicide committed by a patient with schizophrenia on the knowledge about and stigma regarding psychosis among the general Hong Kong population. The effects of using the term 'schizophrenia (jing-shen-fen-lei)' in the news on the perceptions of the new Chinese term 'psychosis (si-jue-shi-tiao)' were explored. METHODS: Random telephone surveys of the general Hong Kong population were conducted in April 2009 (1 month before the incident) and June 2009 (1 week after the incident). Stigma was measured with the Link's Perceived Discrimination-Devaluation Scale (LPDDS). Knowledge about the symptoms, treatment and belief of dangerousness of psychosis were assessed. The emotional reaction of the public to the news was explored, and its effects on knowledge and stigma were studied. RESULTS: Overall, 1016 and 506 participants completed the two surveys. More participants in the post-incident survey agreed that people with psychosis are dangerous to the public (χ2 = 4.934, p = 0.026). However, no significant differences were observed in the LPDDS scores. Participants who reported a high level of distress related to the news were more likely to perceive people with psychosis as dangerous to the public (χ2 = 6.738, p = 0.009). Women and older people reported greater distress. CONCLUSIONS: These findings suggest that media reporting of violent incidents involving people with schizophrenia increases the public belief in the dangerousness of people with psychosis but not the overall stigma. Further studies of the differential effects of violence reporting on public perceptions about people with psychosis and schizophrenia are warranted.

A Randomised, Controlled Study of Different Glycaemic Targets during Gestational Diabetes Treatment: Effect on the Level of Adipokines in Cord Blood and ANGPTL4 Expression in Human Umbilical Vein Endothelial Cells.

Our aim was to study the expression of adipokine-encoding genes (leptin, adiponectin, and angiopoietin-like protein 4 (ANGPTL4)) in human umbilical vein endothelial cells (HUVECs) and adipokine concentration in cord blood from women with gestational diabetes mellitus (GDM) depending on glycaemic targets. GDM patients were randomised to 2 groups per target glycaemic levels: GDM1 (tight glycaemic targets, fasting blood glucose < 5.1 mmol/L and <7.0 mmol/L postprandial, N = 20) and GDM2 (less tight glycaemic targets, <5.3 mmol/L and < 7.8 mmol/L, respectively, N = 21). The control group included 25 women with normal glucose tolerance. ANGPTL4 expression was decreased in the HUVECs from GDM patients versus the control group (23.11 ± 5.71, 21.47 ± 5.64, and 98.33 ± 20.92, for GDM1, GDM2, and controls; p < 0.001) with no difference between GDM1 and GDM2. The level of adiponectin gene expression was low and did not differ among the groups. Leptin gene expression was undetectable in HUVECs. In cord blood, leptin/adiponectin ratio (LAR) was increased in GDM2 compared to controls and GDM1 (p = 0.038) and did not differ between GDM1 and controls. Tight glycaemic targets were associated with normalisation of increased LAR in the cord blood. ANGPTL4 expression was downregulated in HUVECs of newborns from GDM mothers and was not affected by the intensity of glycaemic control.

[EFFECT OF CITOFLAVIN ON THE PARAMETERS OF LIPID PEROXIDATION IN BLOOD PLASMA OF RATS UNDER COLD STRESS CONDITIONS.]

The possibility of correcting free radical oxidation of lipid membranes by the administration of cytoflavin was experimentally studied in rats. It is established that daily cold exposure for 3 h leads to increase in the level of lipid hydroperoxides, diene conjugates, and malonic dialdehyde on the background of decrease in activity of the antioxidant system in the blood of experimental animals. The introduction of cytoflavin (100 mg/kg, i.p.) for 21 day immediately prior to cold exposure leads to reliable (p < 0.05) decrease in the blood level of lipid hydroperoxides (by 13 - 21%), diene conjugates (by 24 - 25%), and malonic dialdehyde (by 20 - 33%) in comparison to rats of the control group. Analysis of the effect of cytoflavin on activity of the antioxidant system components showed that the level of ceruloplasmin and vitamin E in the blood of animals was reliably (p < 0.05) higher by 10 - 33% than analogous indicator in rats of the control group. Thus, the application of cytoflavin under conditions of long-term influence of cold on the organism of animals leads to stabilization of the processes of lipid peroxidation on the background of increased activity of the blood antioxidant system.

ANESTHETIC MANAGEMENT AND INTENSIVE CARE DURING PERIOPERATIVE PERIOD OF ABDOMINAL DELIVERY IN PREGNANT WOMEN WITH PULMONARY ARTERIAL HYPERTENSION.

Background The presence ofpulmonary arterial hypertension (PAH) in pregnant women increases mortality up to 12- 30% and up to 50% when PAH is associated with Eisenmenger syndrome. Due to low prevalence of PAH in pregnancy many aspects ofperioperative management are still unclear. THE AIM: To summarize our approaches to the anesthesia and intensive care in pregnant women with PAH. MATERIALS AND METHODS: 21 pregnant women with PAH (systolic pulmonary artery pressure (SPAP) higher than 60 mm Hg)-who underwent delivery by Caesarean section in 2010 - 2015 were included in the one-centre retrospective study. Data are presented as median (25th, 75th percentile). RESULTS: The median age was 27 (23; 29) years. Among the patients, there were 4 (19%) cases of idiopathic PAH and in 17 (81%) women PAH was associated with congenital heart disease (CHD); 12 (57%) patients'demonstrated Eisenmenger syndrome. Baseline SPAP was 90 (82; 103) mm Hg. SpO2 90 (85,95)%. All women taken PAH-specific therapy (sildenafil) before delivery. Caesarean section (CS) were performed at 32 (28; 34) weeks. In 20 cases CS was perfofined under epidural anesthesia and in one case under general anesthesia due thrombocytopenia. Inhaled nitric oxide (NO) was administered intraoperative to all women in a dose of 40-60 ppm. Postoperative period was uncomplicated in five women (23?8%). Decompensation with PAP rise, acute right ventricular failure and hypoxemia developed in 16 (76,2%) cases 30 (24, 40) h after abdominal delivery. These patients required combined PAH-specific therapy (NO, sldenafil, iloprost) and inotropic agents, additionallyrespiratory support was used in four patients. The median ICU stay was 13 (9; 22) days. 3 patients died (14?2%); mortality in Eisenmenger syndrome cases was 25% (3/12). 18 healthy babies.

Effect of golimumab and pamidronate on clinical efficacy and MRI inflammation in axial spondyloarthritis: a 48-week open randomized trial.

OBJECTIVES: To compare the effect of golimumab (GLM) and pamidronate (PAM) on clinical efficacy and magnetic resonance imaging (MRI) inflammation in axial spondyloarthritis (aSpA). METHOD: Patients who fulfilled the Assessment of SpondyloArthritis Society (ASAS) criteria for aSpA and had active disease [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4] were randomized in a 2:1 ratio to receive either GLM (50 mg) or PAM (60 mg) 4 weekly for 48 weeks. Clinical efficacy was assessed at intervals. Inflammation of the spine and sacroiliac joints (SIJs) on MRI was graded by the Spondyloarthritis Research Consortium of Canada (SPARCC) scoring system. RESULTS: Twenty patients were assigned to GLM and 10 to PAM (83% men; age 33.4 ± 10.9 years; disease duration 4.4 ± 3.4 years). The baseline characteristics of the two groups were similar. At week 48, the proportions of patients who achieved an ASAS20 response were not significantly different between the GLM and PAM groups (65% vs. 56%; p = 0.69). Although there were no differences in BASDAI, spinal pain, and Medical Outcomes Study 36-item Short Form Health Survey (SF-36) scores between the two groups at week 48, the Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath AS Functional Index (BASFI), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were significantly lower in GLM-treated patients. The SPARCC scores of the spine and SIJs decreased significantly in GLM- but not in PAM-treated patients. The differences in SPARCC scores between the two groups at week 48 were statistically significant. The frequency of adverse events (AEs) was similar in both arms. CONCLUSIONS: In patients with aSpA, the clinical response rate and improvement in pain and quality of life (QoL) were similar between GLM and PAM groups after 48 weeks. However, significant reduction in inflammatory markers and MRI inflammation was only observed with GLM treatment.

Uveal Melanoma UK National Guidelines.

The United Kingdom (UK) uveal melanoma guideline development group used an evidence based systematic approach (Scottish Intercollegiate Guidelines Network (SIGN)) to make recommendations in key areas of uncertainty in the field including: the use and effectiveness of new technologies for prognostication, the appropriate pathway for the surveillance of patients following treatment for primary uveal melanoma, the use and effectiveness of new technologies in the treatment of hepatic recurrence and the use of systemic treatments. The guidelines were sent for international peer review and have been accredited by NICE. A summary of key recommendations is presented. The full documents are available on the Melanoma Focus website.

Thermal plasma treatment of stormwater sediments: comparison between DC non-transferred and partially transferred arc plasma.

The disposal of enormous amount of stormwater sediments becomes an emerging worldwide problem. Stormwater sediments are contaminated by heavy metals, phosphorus, trace organic and hydrocarbons, and cannot be disposed without treatment. Thermal plasma decontamination technology offers a high decomposition rate in a wide range of toxic organic compound and immobilization of heavy metal. In this study, we compared the treatment results between two different modes of thermal plasma: (1) a non-transferred direct current (DC) mode and (2) a partial DC-transferred mode. The reductions of total organic carbon (TOC) were, respectively, 25% and 80% for non-transferred and partially transferred plasma, respectively. Most of the toxic organic compounds were converted majorly to CxHy. In the gaseous emission, the accumulated CxHy, CO, NO and H2S were significantly higher in partially transferred mode than in non-transferred mode. The solid analysis demonstrated that the concentrations of Ca and Fe were enriched by 500% and 40%, respectively. New chemical compositions such as KAlSi3O8, Fe3O4, NaCl and CaSO4 were formed after treatment in partially DC-transferred mode. The power inputs were 1 and 10 kW, respectively, for non-transferred DC mode and a partially DC-transferred mode. With a lower energy input, non-transferred plasma treatment can be used for decontamination of sediments with low TOC and metal concentration. Meanwhile, partially transferred thermal plasma with higher energy input is suitable for treating sediments with high TOC percentage and volatile metal concentration. The organic compounds are converted into valuable gaseous products which can be recycled as an energy source.

[General molecular and cellular mechanisms for renal and cardiac remodeling in chronic kidney disease: a target for nephrocardioprotection].

The lecture considers a number of molecular and cellular mechanisms underlying the structural and functional rearrangement and development of renal and cardiac fibrosis in chronic kidney disease (CKD). It details the key component of disadaptative organ remodeling (the formation of myofibroblasts via epithelial-mesenchymal and endothelial-mesenchymal transdifferentiation) and the role of leading angiofibrogenic mediators (angiotensin II, transforming growth factor-beta type 1, a plasminogen activator inhibitor type 1, etc.) in the regulation of these processes. Investigation of the molecular and cellular bases of organ fibrosis, including the factors of dysregulated activation, differentiation and survival of microfibroblasts, makes it possible to specify the mechanisms of action of traditional nephro- and cardioprotective agents, to offer a possibility for a goal-oriented (target) effect on individual fibrogenic components, and to expand the arsenal of medications suppressing renal and cardiac remodeling.

One-step multiplex reverse-transcriptase PCR for detecting pandemic (H1N1) 2009 influenza virus.

Pandemic (H1N1) 2009 influenza has spread throughout the world since April 2009 and has caused many human deaths since its first report in humans. Pandemic (H1N1) 2009 influenza virus was first identified in a Canadian pig herd in April 2009 and has been reported in more than ten countries, including Korea. We developed a one-step multiplex reverse transcriptase polymerase chain reaction (RT-PCR) assay based on the matrix gene that discriminates pandemic (H1N1) 2009 influenza virus from endemic swine influenza viruses. The sensitivity of this assay was 100 copies of in vitro-transcribed target RNA and 0.01 tissue culture infective dose (TCID(50)/ml) of virus and was as high as those of conventional influenza A virus common matrix reverse transcriptase PCR assays and real-time reverse transcriptase PCR assays (1 to 200 copies) developed for detecting pandemic (H1N1) 2009 influenza viruses from human and pig samples. This one-step multiplex RT-PCR assay would be a good tool in monitoring pandemic (H1N1) 2009 influenza virus among pig herds on a regular basis.

Constitutive expression of Vitreoscilla haemoglobin in Sphingomonas elodea to improve gellan gum production.

AIMS: To improve a commercially used strain for gellan production by exogenous Vitreoscilla haemoglobin (VHb). METHODS AND RESULTS: VHb gene was expressed in Sphingomonas elodea under the control of constitutive bla promoter. Biochemical activity of expressed VHb was confirmed by CO-difference spectra analysis that exhibited a characteristic absorption maximum at 419 nm. During cultivation, not only enhanced cell growth was detected, but also 20% improvement in gellan production was observed after 48 h of incubation, with a maximum yield of 16·82 g l(-1). Moreover, maximum sucrose conversion efficiency (g gellan per g sucrose) was 57·8, 20% higher than that of the parental strain. We further examined the polysaccharide production of VHb-expressing strain at different aeration levels in Erlenmeyer flasks. Again, in all cases, a significant enhancement of gellan production was observed, and the enhancement was more significant under oxygen-limiting conditions (up to 26·8%). CONCLUSIONS: VHb exhibited positive effect on cell growth and gellan yield of S. elodea, especially under hypoxic conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first application of VHb as an effective metabolic engineering strategy in S. elodea to regulate cell growth and optimize gellan yield.