Do Hybrid Legal Systems Matter in Foreign Legal-Aid Programmes? Some Philosophical Aspects of Legal Aid in Uzbekistan as Provided by the Donor States

Since the fall of socialism in Eastern Europe, the former Soviet Union, and some states of Southeast Asia, the international financial institutions and individual donor states have initiated wide-scale legal-aid programmes to assist these states in their transition from socialism to a market economy. Whereas the aid from financial institutions vis-à-vis recipient states is often agreed upon specific conditionalities, the donor states design their foreign legal aid according to individual preferences, although sometimes with references to universal goals. Currently, various donor states provide legal aid to Uzbekistan. Given the fact that Uzbekistan is the former Soviet Republic that still bears multiple traces of a socialist legal system and additionally integrates indigenous informal law, this research provides an analysis of how different donor states base their legal-aid activities on entirely different philosophies and levels of gravity, and how receptive the hybrid structure of Uzbekistan’s law is towards such aid.

The global financial safety net: Evolution of the anti-crisis function in the global financial architecture

In the global financial architecture, the functions of anti-crisis support and macroeconomic stabilization are performed by the institutions of the global financial safety net (GFSN). The volume of available financing within the framework of GFNS has grown 10 times over the past decade and reached the equivalent of 4% of world GDP. The literature’s standard understanding of a system of national reserves, swap agreements, regional financial mechanisms, and the IMF requires enlargement. The article proposes the concept of an enlarged global financial safety net, namely by including two new elements — multilateral development banks and bilateral financial support. The manifestations of this phenomenon in many regions of the world are shown in the activities of the largest international development banks and at the level of macroeconomic stabilization financing by individual donor countries, including during the current COVID crisis.

Effect of Leukoreduction on Hematobiochemical Parameters and Storage Hemolysis in Canine Whole Blood Units

Storage lesions (SLs) occur when the red blood cell quality is altered during the preservation of blood units. Pre-storage leukoreduction would limit the number of SLs. The aims of this study were to evaluate the effectiveness of a leukoreduction filter for human use and the effect of pre-storage leukoreduction on some ematobiochemical parameters in stored canine whole blood. Seven canine blood units were tested. Each one was divided into two units—one leukoreduced (LRWB) and one non-leukoreduced (nLRWB). On each unit, we determined the complete blood count (CBC), lactate-dehydrogenase (LDH), electrolytes (Na+, K+, Cl−), morphological index (MI) and hemolysis, on storage days 0, 7, 14, 21, 28, 35, and 42. Leukoreduction allowed a 98.30% recovery of the RBC count, retaining 99.69% and 94.91% of WBCs and PLTs, respectively. We detected a significant increase of LDH and MI with strongly higher values in nLRWB compared to LRWB. A progressive increase in electrolytes and LDH concentrations was observed as indices of stored hemolysis. LDH showed significantly lower values in LRWB units compared to nLRWB, suggesting its release from leukocytes. In the majority of units, hemolysis reached 1% on the 42nd day of storage. We assert the human leukoreduction filter effectiveness on canine whole blood, and we recommend using nLRWB before day 14, especially for critically ill patients. The difference of the basal hemolysis (day 0) percentages observed between subjects suggests that more studies should be performed to confirm a possible inter-individual donor biological variability of RBC membrane resistance, as happens in humans.

Translational Animal Models Provide Insight Into Mesenchymal Stromal Cell (MSC) Secretome Therapy

The therapeutic potential of the mesenchymal stromal cell (MSC) secretome, consisting of all molecules secreted by MSCs, is intensively studied. MSCs can be readily isolated, expanded, and manipulated in culture, and few people argue with the ethics of their collection. Despite promising pre-clinical studies, most MSC secretome-based therapies have not been implemented in human medicine, in part because the complexity of bioactive factors secreted by MSCs is not completely understood. In addition, the MSC secretome is variable, influenced by individual donor, tissue source of origin, culture conditions, and passage. An increased understanding of the factors that make up the secretome and the ability to manipulate MSCs to consistently secrete factors of biologic importance will improve MSC therapy. To aid in this goal, we can draw from the wealth of information available on secreted factors from MSC isolated from veterinary species. These translational animal models will inspire efforts to move human MSC secretome therapy from bench to bedside.

Adipose-Derived Stem Cells from Obese Donors Polarize Macrophages and Microglia toward a Pro-Inflammatory Phenotype

Macrophages and microglia represent the primary phagocytes and first line of defense in the peripheral and central immune systems. They activate and polarize into a spectrum of pro- and anti-inflammatory phenotypes in response to various stimuli. This activation is tightly regulated to balance the appropriate immune response with tissue repair and homeostasis. Disruption of this balance results in inflammatory disease states and tissue damage. Adipose stem cells (ASCs) have great therapeutic potential because of the potent immunomodulatory capabilities which induce the polarization of microglia and macrophages to the anti-inflammatory, M2, phenotype. In this study, we examined the effects of donor heterogeneity on ASC function. Specifically, we investigated the impact of donor obesity on ASC stemness and immunomodulatory abilities. Our findings revealed that ASCs from obese donors (ObASCs) exhibited reduced stem cell characteristics when compared to ASCs from lean donors (LnASCs). We also found that ObASCs promote a pro-inflammatory phenotype in murine macrophage and microglial cells, as indicated by the upregulated expression of pro-inflammatory genes, increased nitric oxide pathway activity, and impaired phagocytosis and migration. These findings highlight the importance of considering individual donor characteristics such as obesity when selecting donors and cells for use in ASC therapeutic applications and regenerative medicine.

Estimating the timing of HIV infection from unmutated sequences

For HIV, the time since infection can be estimated from sequence data for acutely infected samples. One popular approach relies on the star-like nature of phylogenies generated under exponential population growth, and the resulting Poisson distribution of mutations away from the founding variant. However, real-world complications, such as APOBEC hypermutation and multiple-founder transmission, present a challenge to this approach, requiring data curation to remove these signals before reasonable timing estimates may be obtained. Here we suggest a simple alternative approach that derives the timing estimate not from the entire mutational spectrum but from the proportion of sequences that have no mutations. This can be approximated quickly and is robust to phenomena such as multiple founder transmission and APOBEC hypermutation. Our approach is Bayesian, and we adopt a conjugate prior to obtain closed form posterior distributions at negligible computational expense. Using real data and simulations, we show that this approach provides accurate timing estimates and credible intervals without the inconvenience of data curation and is robust to complicating phenomena that can mislead existing approaches or cause them to fail entirely. For immediate use we provide an implementation via Google Sheets, which offers bulk analysis of multiple datasets, as well as more detailed individual-donor analyses. For inclusion in data processing pipelines we provide implementations in three languages: Julia, R, and Python.

Immunoglobulin G of systemic sclerosis patients programs a pro-inflammatory and profibrotic phenotype in monocyte-like THP-1 cells

Objectives Functional IgG autoantibodies against diverse G protein-coupled receptors, i.e. antibodies with agonistic or antagonistic activity at these receptors, are abundant in human serum. Their levels are altered in patients with SSc, and autoantibodies against angiotensin II receptor 1 (ATR1) and endothelin receptor A (ETA) have been suggested to drive SSc by inducing the chemokines CXCL8 and CCL18 in the blood. The objective of our study is to profile the effect of IgG in SSc (SSc-IgG) on the production of soluble mediators in monocytic cells. Methods Monocyte-like THP-1 cells were stimulated with SSc-IgG and their secretome was analysed. Furthermore, the significance of major pro-inflammatory pathways for the induction of CXCL8 and CCL18 in response to SSc-IgG was assessed by a pharmacological approach. Results Stimulation with SSc-IgG significantly alters the secretome of THP-1 cells towards a general pro-inflammatory and profibrotic phenotype, which includes an increase of CCL18 and CXCL8. The consequent expression profiles vary depending on the individual donor of the SSc-IgG. CCL18 and CXCL8 expression is thus regulated differentially, with AP-1 driving the induction of both CCL18 and CXCL8 and the TAK/IKK-β/NF-κB pathway and ERK1/2 driving that of CXCL8. Conclusions Our results suggest that SSc-IgG contributes to the generation of the pro-inflammatory/profibrotic tissue milieu characteristic of SSc by its induction of a respective phenotype in monocytes. Furthermore, our results highlight AP-1 as a critical regulator of gene transcription of CCL18 in monocytic cells and as a promising pharmacological therapeutic target for the treatment of SSc.