On issues related to national risk-based system for control over food products distributed on the market

This research is vital given great significance of food safety for population and bearing in mind that food products are an independent object of sanitary-epidemiologic control as it is stipulated by the legislation. We suggest approaches to creating a risk-based model for control over food products distributed on the market. These ap-proaches involve categorizing food products as per potential health risks for consumers; building up risk profiles of food products; optimizing laboratory support provided for control and surveillance activities taking into account food products safety management. When categorizing food products, risk is assessed as a combination of probable violation of obligatory requirements to safety and severity of consequences these violations might have. Food products that are assigned into extremely high, high and considerable risk categories are subject to systemic control once a year, every two years or every three years accordingly. In case a surveillance object seems “law-abiding’, its category and intensity of control procedures may be changed. Programs for laboratory control over food products are suggested to be based on risk profiles, spotting out priority indicators that make major contributions into risks. Also the approach involves using mathematical models that describe a relation between a number of observations and an expected answer (as a reduction in quantities of deviating samples at the next stage in the control cycle). This model determines how many samples of priority indicators should be tested in order to achieve a target risk level. It also allows predict an expected number of violations and health risk rates at the next stage in the control cycle given the present number of observations. 85 regional registers of food products were created and categories were determined as per health risks for all groups of food products under surveillance. It was shown that in some cases it was necessary to increase a number of observations over priority (“risky”) indicators in order to detect hazardous products and withdraw them from the market. Certain examinations seem redundant as they don’t play any role in making control procedures more efficient. The suggested approaches are universal and dynamic. Basic trends in the model development may include more targeted selection of products for control; risk profiles creations and systemic actualization; further development of laboratory support for control (surveillance) given that the food products market is changing dynamically in the country.

Primary Extramedullary Plasmacytoma of the Kidney: A Case Report and Literature Review

Extramedullary plasmacytomas (EMPs) usually occur in the upper respiratory tract, the occurrence in the kidney is extremely rare. The present study reported a case of primary renal plasmacytoma in a 46‑year‑old male patient with frequent and urgent urination, nocturia increased due to renal failure. Computed tomography (CT) imaging showed a 60×58mm enhanced mass at the lower pole of the right kidney. Following the radical nephrectomy, histopathological and immunohistochemistry analysis of the resected specimen supported the diagnosis of plasmacytoma. Bone marrow biopsy and total body skeletal survey was performed to demonstrate that there were no evidence of multiple myeloma (MM) and bone lesions. Consequently, a diagnosis of a primary renal EMP was proposed. Subsequently, the patient was treated with 4 course of chemotherapy VAD (vincristine, epirubicin and dexamethasone) + cyclophosphamide + thalidomide, and he was disease-free during 4 years’ follow-up time. The current study also presents a review of the literatures. Treatment of primary renal EMP is surgery, radiotherapy, chemotherapy or a combination of those, even hematopoietic stem cell transplantation may be also an option. Long-term follow-up is a necessity for systemic control due to the possibility to transform into MM.

PARS PLANA VITRECTOMY FOR VITREOUS HEMORRHAGE IN CIPTOMANGUNKUSUMO HOSPITAL

Introduction: Vitreous hemorrhage is the presence of blood in the vitreous cavity. This condition could impair the visual function and hindered the clinician’s ability to examine the posterior segment of the eye. Pars plana vitrectomy (PPV) not only act as a surgical treatment of choice but also diagnostic procedure. Immediate PPV has the advantage to optimalize visual acuity Methods: Retrospective descriptive study of vitreous hemorrhage patients underwent pars plana vitrectomy in Ciptomangunkusumo Hospital, Indonesia from January to December 2018 Result: There were 160 cases of vitreous hemorrhage cases undergoes pars plana vitrectomy in 2018. Most frequent etiology was proliferative diabetic retinopathy (49.4%). Rebleeding was found only in 8 cases within the period of three months follow up. Final visual acuity was improved in majority of the cases and found to be related to timing of the surgery. Conclusion: Early vitrectomy along with systemic control of underlying factors lead to improvement of visual acuity in vitreous hemorrhage.

Systemic control of nodule formation by the plant N demand requires autoregulation dependent and independent mechanisms

In legumes interacting with rhizobia the formation of symbiotic organs involved in the acquisition of atmospheric nitrogen is depending of the plant nitrogen (N) demand. We used Medicago truncatula plants cultivated in split-root systems to discriminate between responses to local and systemic N signalings. We evidenced a strong control of nodule formation by systemic N-signaling but obtained no clear evidence of a local control by mineral nitrogen. Systemic signaling of the plant N demand controls numerous transcripts involved in the root transcriptome reprogramming associated to early rhizobia interaction and nodule formation. SUNN has an important role in this control but major systemic N signaling responses remained active in the sunn mutant. Genes involved in the activation of nitrogen fixation are regulated by systemic N signaling in the mutant, explaining why the hypernodulation phenotype is not associated to a higher nitrogen fixation of the whole plant. The control of the transcriptome reprogramming of nodule formation by systemic N signaling requires other pathway(s) that parallel the SUNN/CLE pathway.

Pulsed Radiation Therapy to Improve Systemic Control of Metastatic Cancer

Radiation therapy (RT) is emerging as an interventional modality in the cancer-immunity cycle, augmenting the activation of an adaptive immune response against tumors. RT, particularly in combination with immunotherapy, can enhance immune memory effects and shape the tumor-directed T-cell populations. However, a single cycle of RT delivered to a limited number of polymetastatic lesions is rarely sufficient to achieve systemic control. We hypothesize that several rounds of RT, akin to several rounds of immunotherapeutic drugs, is likely to provide greater clinical benefit to patients with metastatic disease. We propose that the repeated exposure to tumor antigens released by “pulsed-RT” (i.e., treating 2-4 tumor lesions with 3 irradiation cycles given one month apart) may amplify the adaptive immune response by expanding the tumor-specific T-cell receptor repertoire, the production of high-affinity tumor antibodies, and the generation of memory lymphocytes and thereby improve immune control of systemic disease.

Pseudo-Media Sites, Polarization, and Pandemic Skepticism in Spain

The Coronavirus pandemic has triggered an authentic infodemic, which is a global epidemic of disinformation that has spread throughout most of the world. Social media platforms and pseudo-media outlets have contributed to the problem by producing and disseminating misleading content that is potentially dangerous to public health. This research focuses on a rather unknown phenomenon, which involves digital sites that mimic the appearance of news media but provide pseudo-information. Five Spanish pseudo-media have been analyzed with the aim of enhancing understanding of the issues and the frames presented. The results show clear links with the far-right ideology as well as the presence of a populist, polarized discourse through the use of belligerent, offensive expressions to refer to institutions and their representatives. Politics is the main issue represented, with a frame that clearly points out the incompetence and cynicism of the Spanish government. Conspiracy theories associate the origins of the pandemic to a Chinese laboratory and emphasize a global plan to establish systemic control. Measures to stop the virus are framed as harmful and ineffective, linked to a euthanasia scheme targeted at older people, especially regarding vaccination, which is presented as a solution offered for economic interests.

Overcoming resistance to anti-PD-1 with tumor agnostic NBTXR3: From bench to bed side.

2591 Background: Despite recent advances, resistance to immune checkpoint inhibitors (ICI), observed in over 80% of treated patients, is currently the main challenge in immuno-oncology. Intense efforts are being made to identify combination therapies that could improve ICI response rates. NBTXR3, a novel radioenhancer administered by direct intratumoral injection (ITI), is designed at the nanoscale to increase radiation therapy (XRT) dose deposit within tumor cells and subsequent tumor cell killing, without increasing toxicity to surrounding healthy tissue. Here we present evidence that NBTXR3 activated by XRT primes the immune system, producing an anti-tumor response, including activation of the cGAS-STING pathway, that overcomes anti-PD-1 resistance both in mice models and patients. Methods: Abscopal assays were conducted in immunocompetent mice. Anti-PD-1 sensitive or resistant tumor cell lines, were injected in both flanks of mice. Intratumoral injection of NBTXR3 (or vehicle) followed by XRT was performed in right flank (primary) tumors only. Some mice also received anti-PD-1 injections. Tumor growth was monitored, and tumor immune cell infiltrates analyzed by immunohistochemistry (IHC). Separately, in the phase II/III randomized Act.in.Sarc [NCT02379845] trial patients with locally advanced soft tissue sarcoma (STS) received either NBTXR3+XRT or XRT alone followed by tumor resection. Pre- and post-treatment tumor samples from patients in both groups were analyzed by IHC and Digital Pathology for immune biomarkers. The safety and efficacy (RECIST 1.1/iRECIST) of NBTXR3 plus stereotactic body radiotherapy (SBRT) in combination with anti-PD-1 is being evaluated in three cohorts of patients with advanced cancers [NCT03589339]. Results: Pre-clinical studies demonstrated that NBTXR3+XRT induces an immune response not observed with XRT alone and enhances systemic control. IHC showed significant increase of CD8+ T-cell infiltrates in both NBTXR3+XRT treated and untreated tumors compared to XRT alone. Similarly, increased CD8+ T-cell and decreased FOXP3+ Treg density (pre- vs post-treatment) was observed in tumor tissues from STS patients treated with NBTXR3+XRT. Furthermore, NBTXR3+XRT in combination with anti-PD-1 improved local and systemic control in mice bearing anti-PD-1 resistant lung tumors, as well as reduced the number of spontaneous lung metastases. Preliminary efficacy data from the first in human trial of NBTXR3+XRT in combination with anti-PD-1 showed tumor regression in the majority of patients (8/9). Of note, tumor regression was observed in 6/7 pts who had progressed on prior anti-PD-1. Conclusions: The clinical efficacy of NBTXR3+XRT has been demonstrated as a single agent. We now demonstrate that it potentiates anti-PD-1 treatment to overcome resistance mechanisms. These results highlight the potential of NBTXR3+XRT to positively impact the immuno-oncology field. Clinical trial information: NCT03589339.

Monitoring as one of the forms of control over recipients of budget funds

Departmental control is an integral part of the financial management system. Improvement of the financial management system — the system of management of state (public) finances inevitably brings the task of improving the system of departmental control. Transition to the system of budget formation and spending based on the result-oriented principle sets a task for departmental control to implement systemic control over the achievement of performance indicators. Particularities of the order of formation, execution and performance reports of targets resulted in the development of specifics of monitoring and control procedures that go beyond the concept of financial control. The system of multilevel control, which includes monitoring of natural indicators achievement has been proposed, and the algorithm for monitoring has been developed.

Deiodinases and Cancer

Hormones are key drivers of cancer development, and alteration of the intratumoral concentration of thyroid hormone (TH) is a common feature of many human neoplasias. Besides the systemic control of TH levels, the expression and activity of deiodinases constitute a major mechanism for the cell-autonomous, prereceptoral control of TH action. The action of deiodinases ensures tight control of TH availability at intracellular level in a time- and tissue-specific manner, and alterations in deiodinase expression are frequent in tumors. Research over the past decades has shown that in cancer cells, a complex and dynamic expression of deiodinases is orchestrated by a network of growth factors, oncogenic proteins, and miRNA. It has become increasingly evident that this fine regulation exposes cancer cells to a dynamic concentration of TH that is functional to stimulate or inhibit various cellular functions. This review summarizes recent advances in the identification of the complex interplay between deiodinases and cancer and how this family of enzymes is relevant in cancer progression. We also discuss whether deiodinase expression could represent a diagnostic tool with which to define tumor staging in cancer treatment or even a therapeutic tool against cancer.

Autoregulation dependent and independent mechanisms are responsible for the systemic control of nodule formation by the plant N demand

In legumes interacting with rhizobia the formation of symbiotic organs responsible for the acquisition of atmospheric nitrogen is depending of the plant nitrogen (N) demand. We discriminated between local and systemic impact of nitrogen on nodule formation using Medicago truncatula plants cultivated in split-root systems. We obtained evidence of the control of nodule formation by whole plant systemic N-satisfaction signaling but obtained little evidence of a local control by mineral nitrogen. We characterized the impact of systemic N signaling on the root transcriptome reprogramming associated to nodule formation. We identified, large genes clusters displaying common expression profiles in response to systemic N signaling enriched in particular fonctions required during these biological processes. We found evidence of a strong effect of SUNN in the control by systemic N signaling of many genes involved in the early interaction with rhizobium as well as organogenesis supporting a role of autoregulation pathway in systemic N signaling. However, we also found evidence that major SUNN independent systemic N signaling controls were maintained in the mutant. This study shed light on the unexpected high complexity of the control of nodule formation by systemic N signaling, that probably involves multiple pathways.