Evaluation of hyperthermic intraperitoneal chemotherapy (HIPEC) in reducing metachronous peritoneal metastases (MPM) risks in patients with resectable serosa-invasive gastric cancer.
Between 2008 and ...2016, 154 patients with gastric cancer (stage IIB-IIIC) were randomly assigned to two groups: 76 patients underwent HIPEC (cisplatin 50 mg/m2 + doxorubicin 50 mg/m2, 42 °C, 1 h) combined with radical surgery (HIPEC group) and 78 patients underwent only radical surgery (control group).
Evaluation of HIPEC toxicity showed neither toxic complications of IV-V degree nor haematological toxicity (according to CTCAE v. 4.03). There was no significant difference in the rate of complications between the two groups (p = 0.254). There was a more frequent disease progression in the control group than in the HIPEC group: 42/55 patients (76.4%) vs. 36/68 patients (52.9%), respectively (p = 0.009). At the same time a significant decrease in the rate of MPM was observed after HIPEC administration as compared with surgery alone – 16/68 (12.8%) vs. 39/55 (27.6%) (p < 0.001). 3-year progression-free survival was 47% (95% CI 36–61)) in the HIPEC group and 27% (95% CI 17–43) in the control group – p = 0.0024.
The N-stage, HIPEC procedure, type of surgery and interaction between HIPEC treatment and age were independent prognostic factors.
HIPEC appears to be helpful in improving treatment results in radically operated gastric cancer patients.
Hyperthermic intraperitoneal chemotherapy (HIPEC) appears to be helpful in decreasing risks of metachronous peritoneal metastases (MPM) and has a potential for improving the survival rate in radically operated gastric cancer patients. HIPEC administration made it possible to attain a statistically significant reduction in the cumulative incidence of MPM.
The aim of the work was to determine the cytotoxicity and the influence of polycyclic derivatives of the framework series on the replicative properties of the SARS-CoV-2 virus in Vero-E6 cell culture ...in vitro. Materials and methods . The virus inhibiting effect of 50 adamantane and bicyclo3.3.1nonane derivatives with carbocyclic and heterocyclic substituents was investigated. The studies were carried out on Vero-E6 cell culture by assessing the cytopathic effect of the virus. The impact of the compounds on the replicative properties of the SARS-CoV-2 virus was estimated by the decrease in virus titer in the presence of the compounds compared to the control. Based on the virus titer values in the presence of a series of successively decreasing concentrations of the compound, the 50 % effective concentration was calculated. Results and discussion . A study of polycyclic derivatives of the framework series has identified two compounds with antiviral properties against the SARS-CoV-2 virus. Among bicyclo3.3.1nonane derivatives containing heterocyclic fragments, compound No. 15144 has showed an inhibitory effect against the SARS-CoV-2 virus. The protective effect of the compound was manifested in maximum tolerable concentration (MTC) (70.0 μg/ml) and ½ MTC (35.0 µg/ml). A decrease in virus titers under the influence of MTC by 0.95 lg TCD 50 /ml, in ½ MTC (35.0 μg/ml) – by 0.35 lg TCID 50 /ml has been detected. The effective concentration (EC50) value of the compound No. 15144 was 64.0 μg/ml, the MTC/EC50 ratio was 1.09. Compound No. 14838 (adamantane derivative containing carbocyclic fragments) had less pronounced antiviral activity. As a result of research, it has been established that sample No. 14838 at a dose of MTC (45.0 μg/ml) reduces the infectious titer by 0.78 lg TCD 50 /ml, in ½ MTC (22.5 μg/ml) by 0.15 lg TCD 50 /ml compared to the control. The EC50 value of compound No. 14838 was 37.0 μg/ml, the MTC/EC50 ratio was 1.22.
The most important component of strengthening the potential for responding to biological threats both at the national and interstate levels is the formation of a unified system for monitoring and ...responding to emergencies (ES) of sanitary-epidemiological nature in the CIS territory.
The aim
of the work was to review the systems for monitoring and responding to emergencies of sanitary-epidemiological character in the CIS countries by the example of the Russian Federation, the Republic of Belarus, the Republic of Kazakhstan and the Kyrgyz Republic, to characterize the main areas of international cooperation on countering biological threats and coordinating international response measures in the CIS countries.
Materials and methods
. Information and analytical materials provided by organizations responsible for epidemiological surveillance and control in the CIS countries, Internet sources, and publications were used for the study.
Results and discussion
. The organization and functioning of the systems for monitoring and responding to emergencies in the CIS countries is a state function. It includes, as a rule, the national, regional (sub-national) and territorial (local) levels, which have horizontal and vertical connections. The legal framework is made up of documents of the legislative level. Interdepartmental interaction in response to emergencies is carried out both at the republican level and in administrative territories; the basis for interaction is the integrated planning of preventive and anti-epidemic measures and the functioning of the relevant organizational structures on an ongoing basis. Since 2015, with the support of the Government of the Russian Federation, programs have been implemented aimed at assisting partner countries in the implementation of the International Health Regulations (2005) in order to increase national response capacity and form a unified sanitaryepidemiological emergency response system in the CIS countries. The main areas of collaboration are strengthening the material and technical base and human resources of specialized institutions and scientific cooperation. As a result of the program implementation, a unified system for monitoring and prompt response to emergencies in the field of public health of sanitary-epidemiological nature has essentially been formed in the CIS countries to date, uniting more than 15 specialized institutions from 8 CIS countries.
Lab-on-a-chip (LOC) forms the basis of new-generation portable analytical systems. LOC allows the manipulation of ultralow flows of liquid reagents and multistep reactions on a microfluidic chip, ...which requires a robust and precise instrument to control the flow of liquids on a chip. However, commercially available flow meters appear to be a standalone option adding a significant dead volume of tubes for connection to the chip. Furthermore, most of them cannot be fabricated within the same technological cycle as microfluidic channels. Here, we report on a membrane-free microfluidic thermal flow sensor (MTFS) that can be integrated into a silicon-glass microfluidic chip with a microchannel topology. We propose a membrane-free design with thin-film thermo-resistive sensitive elements isolated from microfluidic channels and a 4′′ wafer silicon-glass fabrication route. It ensures MTFS compatibility with corrosive liquids, which is critically important for biological applications. MTFS design rules for the best sensitivity and measurement range are proposed. A method for automated thermo-resistive sensitive element calibration is described. The device parameters are experimentally tested for hundreds of hours with a reference Coriolis flow sensor demonstrating a relative flow error of less than 5% within the range of 2-30 μL min
−1
along with a sub-second time response.
Design, electronics, fabrication technology, and characterization method of an on-chip corrosion-resistant microfluidic thermal flow sensor for silicon lab-on-a-chip and POC devices.
Alzheimer's disease (AD) is a progressive neurologic disease and the most common cause of dementia. Classic pathology in AD is characterized by inflammation, abnormal presence of tau protein, and ...aggregation of β-amyloid that disrupt normal neuronal function and lead to cell death. Deficits in communication also occur during disease progression and significantly reduce health, well-being, and quality of life. Because clinical diagnosis occurs in the mid-stage of the disease, characterizing the prodrome and early stages in humans is currently challenging. To overcome these challenges, we use the validated
(F344-Tg(Prp-APP, Prp-PS1)19/Rrrc) transgenic rat model that manifests cognitive, behavioral, and neuropathological dysfunction akin to AD in humans.
The overarching goal of our work is to test the central hypothesis that pathology and related behavioral deficits such as communication dysfunction in part manifest in the peripheral nervous system and corresponding target tissues already in the early stages. The primary aims of this study are to test the hypotheses that: (1) changes in ultrasonic vocalizations (USV) occur in the prodromal stage at 6 months of age and worsen at 9 months of age, (2) inflammation as well as AD-related pathology can be found in the thyroarytenoid muscle (TA) at 12 months of age (experimental endpoint tissue harvest), and to (3) demonstrate that the
rat model is an appropriate model for preclinical investigations of early AD-related vocal deficits.
USVs were collected from male
(
= 19) and wildtype (WT)
rats (
= 19) at 6 months (
= 38; WT:
= 19;
:
= 19) and 9 months of age (
= 18; WT:
= 10;
:
= 8) and acoustically analyzed for duration, mean power, principal frequency, low frequency, high frequency, peak frequency, and call type. RT-qPCR was used to assay peripheral inflammation and AD-related pathology via gene expressions in the TA muscle of male
rats (
= 6) and WT rats (
= 6) at 12 months of age.
This study revealed a significant reduction in mean power of ultrasonic calls from 6 to 9 months of age and increased peak frequency levels over time in
rats compared to WT controls. Additionally, significant downregulation of AD-related genes
,
,
, and
as well as downregulation of pro-inflammatory gene
was found in the TA muscle of
rats at 12 months of age.
Our findings demonstrate early and progressive vocal deficits in the
rat model. We further provide evidence of dysregulation of AD-pathology-related genes as well as inflammatory genes in the TA muscles of
rats in the early stage of the disease, confirming this rat model for early-stage investigations of voice deficits and related pathology.
Gastric cancer progression resulting in metachronous peritoneal metastasizing is almost always associated with an adverse prognosis. This review discusses various options of preventing metachronous ...peritoneal metastases in radically operated gastric cancer patients. Also examined are different hyperthermic intraperitoneal chemotherapy (HIPEC) regimens employed in gastric cancer treatment, postoperative morbidity and mortality rates and long-term treatment outcomes. The authors also review their own experience of using HIPEC based on the combination of cisplatin and doxorubicin in doses of 50 mg/m
at 42 °C for 1 h to prevent gastric cancer peritoneal dissemination. As a result, progression-free survival rose from 19.6%±5.6% to 47.1%±6.3% (P
<0.001) and dissemination-free survival-from 22.7%±6.0% to 51.9%±6.3% (P
<0.001). It is noted that the combination of the described HIPEC regimen with systemic chemotherapy helped raise metastases-free 3-year survival rate to up to 91.0%±9.0% (P
=0.025) compared with 48.6%±6.4% for patients who underwent only a combined surgery/HIPEC treatment. HIPEC is a promising combined treatment strategy for radically operated gastric cancer patients that can improve patient survival and decrease peritoneal dissemination rate. However, the number of randomized studies on adjuvant HIPEC are still insufficient for a subgroup assessment of efficacy of the given chemotherapy regimens and generation of evidence-based recommendations on the individual use of chemotherapy agents and their combinations, and HIPEC procedural techniques. Further prospective randomized studies are needed to assess the practicability of complementing HIPEC with adjuvant systemic chemotherapies.
Two plasmid vectors, which allow the recombinant polypeptides of Lassa and Marburg viruses to be expressed in prokaryotic cells E. coli strain BL21 (DE3), were produced. The two recombinant ...polypeptides are able to bind specific antibodies. This provides an opportunity to use them as antigenic components of immunoassay diagnostic test kits.
PDF
