Intravenous hMSCs Improve Myocardial Infarction in Mice because Cells Embolized in Lung Are Activated to Secrete the Anti-inflammatory Protein TSG-6

SummaryQuantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (i.v.) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 × 106 hMSCs were i.v. infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr, but <1000 cells appeared in six other tissues. The hMSCs in lung upregulated expression of multiple genes, with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, i.v. hMSCs, but not hMSCs transduced with TSG-6 siRNA, decreased inflammatory responses, reduced infarct size, and improved cardiac function. I.v. administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest that improvements in animal models and patients after i.v. infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6

Lineage Regulators Direct BMP and Wnt Pathways to Cell-Specific Programs during Differentiation and Regeneration

SummaryBMP and Wnt signaling pathways control essential cellular responses through activation of the transcription factors SMAD (BMP) and TCF (Wnt). Here, we show that regeneration of hematopoietic lineages following acute injury depends on the activation of each of these signaling pathways to induce expression of key blood genes. Both SMAD1 and TCF7L2 co-occupy sites with master regulators adjacent to hematopoietic genes. In addition, both SMAD1 and TCF7L2 follow the binding of the predominant lineage regulator during differentiation from multipotent hematopoietic progenitor cells to erythroid cells. Furthermore, induction of the myeloid lineage regulator C/EBPα in erythroid cells shifts binding of SMAD1 to sites newly occupied by C/EBPα, whereas expression of the erythroid regulator GATA1 directs SMAD1 loss on nonerythroid targets. We conclude that the regenerative response mediated by BMP and Wnt signaling pathways is coupled with the lineage master regulators to control the gene programs defining cellular identity

SAFETY AND EFFECTIVENESS OF INTRAARTICULAR ADMINISTRATION OF ADIPOSE-DERIVED STROMAL VASCULAR FRACTION FOR TREATMENT OF KNEE ARTICULAR CARTILAGE DEGENERATIVE DAMAGE: PRELIMINARY RESULTS OF A CLINICAL TRIAL

The incidence of knee osteoarthritis tends to increase every year and constitutes more than 83% of overall OA morbidity. Moreover, the OA morbidity among younger patients is also increasing. However, currently available treatment methods do not provide quite satisfactory outcomes.Purpose of the study – to evaluate safety and efficacy of intraarticular introduction of autologous adipose-derived stromal vascular fraction for treatment of knee osteoarthritis.Material and methods. By the moment of writing the present report, 28 patients were included into the study. All patients underwent tumescent liposuction under local anesthesia. The stromal vascular fraction was isolated from lipoaspirate within 1,5 hours after harvesting and subsequently injected into the articular cavity. Follow-up period was 6 months after injections. The authors report on efficacy data of 10 patients who completed the study according to protocol and safety data of all 28 patients. Efficacy was evaluated basing on laboratory assessments and patient’s subjective assessment by validated questionnaires.Results. Neither adverse reactions no adverse events were observed. Significant decrease of pain severity by VAS was noted in one week after injection and pain score continued decreasing during the whole follow up period. The increase of KOOS score was noted starting on the fifth week after injection. KSS part 1 score increased in 8 weeks, KSS part 2 score — in 6 months after injection. Physical health, assessed with SF-36 questionnaire significantly improved in 2 and 6 months after the procedure. There was a clear trend towards improvement of mental health.Conclusion. Preliminary results of clinical study suggest intraarticular injection of autologous adipose-derived stromal vascular fraction to be a safe and efficient method of the treatment of knee osteoarthritis

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Low aquaporin-2 excretion in the nephrotic syndrome: an escape from the vasopressin regulating effect

Mikhail Brovko,1 Lidia Kozlovskaya,1 Andrey Pulin,1,2 Sergey Moiseev,1 Victoria Sholomova,1 Dmitry Shchekochikhin,1 Daria Gognieva,1 Ludmila Milovanova,1 Victor Fomin1 1Sechenov First Moscow State Medical University, Moscow, Russia; 2Laboratory for Cell Technologies and Developmental Pathology, Federal State Budgetary Scientific Institution &ldquo;Institute of General Pathology and Pathophysiology,&rdquo; Moscow, Russia Purpose: Experimental studies suggest that the nephrotic syndrome is associated with &ldquo;vasopressin escape&rdquo;, characterized by low aquaporin-2 (AQP2) expression in the collecting duct despite high vasopressin secretion. We investigated this phenomenon in patients with the nephrotic syndrome. Patients and methods: We recruited 47 patients with proteinuric kidney disease who were distributed into the following four groups: 1) nephrotic syndrome with kidney dysfunction (n=10); 2) nephrotic syndrome with normal kidney function (n=16); 3) partial remission of nephrotic syndrome (n=10); and 4) minimal proteinuria (n=11). Nine healthy volunteers comprised a control group. Serum copeptin level (as a marker of vasopressin secretion) and urinary AQP2 were measured using ELISA. Results: Nephrotic syndrome was associated with a significant increase in serum copeptin levels compared with those in the other groups (all P&lt;0.05). In patients with nephrotic syndrome and a partial remission of nephrotic syndrome combined, there was more than a ten-fold decrease in the median urinary AQP2 excretion (0.03 ng/mL) compared with healthy volunteers (0.41 ng/mL; P&lt;0.001) and more than a five-fold decrease compared with patients with minimal proteinuria (0.21 ng/mL; P&lt;0.05). Unlike copeptin levels, the median urinary AQP2 excretion in patients with minimal proteinuria also decreased but less significantly than in those with nephrotic syndrome. There was a negative correlation between the urinary AQP2 excretion and daily proteinuria (R=&minus;0.41; P=0.005). Conclusion: Our clinical study was the first to demonstrate low AQP2 excretion in nephrotic syndrome that may indicate an escape from the vasopressin regulating effect. Keywords: nephrotic syndrome, aquaporin-2, copeptin, vasopressin escap

DETECTOR OF NEUTRON-AND GAMMA-RADIATIONS

FIELD: for dosimetric and customs practice, for solution of the problems of the State Atom Inspection and services of nuclear safety, for complexes and systems of special radiation technical control, and radiation monitoring of territories and water areas, for detection and identification of fissionable materials.SUBSTANCE: the detector has three transducers that are used for detection of quick, intermediate and heat neutrons, as well as for detection of gamma-radiation. The transducers are located in a common casing. PIN-sensor elements are used as transducers, they are placed in bags of boron-containing radiator-converter of neutrons made of carbide or boron nitride. The first and second transducers have inhibitors in the form of layers of hydrogen-containing material, the shape of the above inhibitors and the shape of the above radiators converters are of a variable cross-section.EFFECT: enhanced accuracy of detection of gamma-radiation, expanded measurement range.1 dwg.Использование: для дозиметрической и таможенной практики, для решения задач Госатомнадзора и служб ядерной безопасности, для комплексов и систем специального радиационного технического контроля и радиационного мониторинга территорий и акваторий, для обнаружения и идентификации делящихся материалов. Сущность: детектор содержит три датчика, которые служат для регистрации быстрых, промежуточных и тепловых нейтронов, а также для регистрации гамма-излучения. Датчики размещены в едином корпусе. В качестве датчиков используются PIN-сенсорные элементы, которые помещены в чехлы из борсодержащего радиатора-конвертора нейтронов, изготовленные из карбида или нитрида бора. Первый и второй датчики содержат замедлители в виде слоев водородсодержащего материала, причем форма вышеупомянутых замедлителей и форма вышеупомянутых радиаторов-конверторов имеет переменное сечение. Технический результат: повышение точности регистрации гамма-излучения, расширение диапазона измерений. 1 ил

SCINTILLATION DETECTOR OF NEUTRON AND GAMMA RADIATION

FIELD: radiation monitoring. SUBSTANCE: scintillation detector can be used in custom houses, units of State Atomic Supervision, in systems of special radiation monitoring of nuclear submarines subject to stripping, in detection and identification of fissionable materials ( uranium, plutonium, californium ) and articles from them, and materials related to class of radioactive substances-gamma radiation sources. Scintillation detector of neutron and gamma radiation includes sensor coming in the form of two scintillators connected in parallel: external neutron scintillator based on plastic material (CH)n or stilbene ( scintillator with well ) placed into jacket of boroncarrying (boron nitride or carbide ) material and internal scintillation crystal Nal-T1 located in well of external scintillator in standard container and sensitive to gamma radiation, photoelectron multiplier positioned in jacket of boron nitride or carbide ( natural mixture of isotopes of boron or isotope 105B ) sensitive to thermal neutrons placed in single case and unit of electron processing of signals. EFFECT: provision for counting neutrons of wide spectrum of energy, both fast and thermal neutrons, with raised efficiency. 1 cl, 1 dwg, 1 tbl.Использование: в дозиметрической таможенной практике, для решения задач Госатомнадзора, для систем радиационного мониторинга и систем специального радиационного технического контроля для обследования ядерных субмарин, подлежащих разборке, для обнаружения и идентификации делящихся материалов (урана, плутония, калифорния и изделий из них) и материалов, относящихся к классу радиоактивных веществ - гамма-источников. Сущность: сцинтилляционный детектор нейтронов и гамма-излучения содержит датчик, выполненный в виде двух параллельно соединенных сцинтилляторов: внешнего нейтронного сцинтиллятора на основе пластмассы (СН)n или стильбена (сцинтиллятор с колодцем), расположенного в чехле из борсодержащего (нитрида или карбида бора) материала, и размещенного в нем (в колодце внешнего сцинтиллятора) чувствительного к гамма-излучению внутреннего сцинтилляционного кристалла NaI-Tl в стандартном контейнере, также расположенного в чувствительном к тепловым нейтронам чехле из нитрида или карбида бора (естественная смесь изотопов бора или изотоп 10?5В), фотоэлектронного умножителя, помещенных в единый корпус, и блок электронной обработки сигналов. Технический результат: обеспечение счета нейтронов широкого спектра энергий как быстрых, так и тепловых с повышенной эффективностью. 1 з.п. ф-лы, 1 ил., 1 табл