Programmed cell death-1 and its ligands: Current knowledge and possibilities in immunotherapy

Programmed Cell Death-1 (PCD-1) is a key immune checkpoint receptor, which mainly expresses on activated T, B, Dendritic (DC), Natural Killer (NK), and Treg cells. On the surface of activated T-cells, PCD-1 expression is upregulated after the recognition of peripherals antigens by T cells; subsequently, the elevated binding of PD-1 to Programmed Death Ligand-1 (PD-L1) and Programmed Death Ligand-2 (PD-L2) becomes a key step for downstream inhibitory signaling. Although the role of PD-L1 has been evaluated more thoroughly by clinical research, and PD-L1 has also been used more widely in the clinical setting, PD-L2 also plays an important role in the negative regulation of T-cells, one of the necessary conditions that lead to immune tolerance. Expression of PD-L1 either in tumors or in infiltrating immune cells has been verified predominantly by Immunohistochemistry (IHC) in a variety of tumors, suggesting a role for the PD-1/PD-L1 axis as a prognostic trait and therapeutic target across multiple histotypes. The complex interplay between these factors plays a major role in the diffusion and clinical application of PD-L1 IHC assays as predictive biomarkers of response to PD-1/PD-L1 inhibitors. Checkpoint blockades are registered for the treatment of various cancers, including gynecological malignancies

Endocytosis and lysosomal degradation of GluA2/3 AMPARs in response to oxygen/glucose deprivation in hippocampal but not cortical neurons

Abstract Global cerebral ischemia results in oxygen and glucose deprivation (OGD) and consequent delayed cell death of vulnerable neurons, with hippocampal CA1 neurons more vulnerable than cortical neurons. Most AMPA receptors (AMPARs) are heteromeric complexes of subunits GluA1/GluA2 or GluA2/GluA3, and the presence of GluA2 renders AMPARs Ca2+-impermeable. In hippocampal CA1 neurons, OGD causes the synaptic expression of GluA2-lacking Ca2+-permeable AMPARs, contributing to toxic Ca2+ influx. The loss of synaptic GluA2 is caused by rapid trafficking of GluA2-containing AMPARs from the cell surface, followed by a delayed reduction in GluA2 mRNA expression. We show here that OGD causes endocytosis, lysosomal targeting and consequent degradation of GluA2- and GluA3-containing AMPARs, and that PICK1 is required for both OGD-induced GluA2 endocytosis and lysosomal sorting. Our results further suggest that GluA1-containing AMPARs resist OGD-induced endocytosis. OGD does not cause GluA2 endocytosis in cortical neurons, and we show that PICK1 binding to the endocytic adaptor AP2 is enhanced by OGD in hippocampal, but not cortical neurons. We propose that endocytosis of GluA2/3, caused by a hippocampal-specific increase in PICK1-AP2 interactions, followed by PICK1-dependent lysosomal targeting, are critical events in determining changes in AMPAR subunit composition in the response to ischaemia

Leadership and motivation among employees in health-care facilities in Serbia

Reserarch question: This paper investigates whether motivational factors have influence on the work of employees in health care organizations of Serbia and what factors affect employees. Motivation: Motivation and job satisfaction among different groups of workers in health care facilities in Serbia are an important issue. This study’s purpose is to assist health managers in their efforts to fulfill individual and organizational targets by highlighting the most preferred motivational factors among the employees. With good leadership and with the building of good motivational system the organization can increase its value and competitiveness. It has been shown that employees are more motivated and work under less stress if there is a support from their leader or manager (Jensen, 2010). Idea: The  core  idea  of  this  paper  is to  evaluate  the  relationship  between motivational factors and work of employees in health care institutions in Serbia. The central hypothesis of this study is what the managers within health care institutions have to do to improve motivation as well as their abilities for the fulfillment of both individual’s and organization’s needs. Data: The cross-sectional study included 217 physicians, nurses, technicians, health associates and non-medical staff in 21 facilities of primary, secondary and tertiary levels in Pozarevac, Belgrade, Nis, Pirot, Novi Sad, Zrenjanin, Krusevac, Varvarin and Novi Pazar. Tools: The research instrument was a questionnaire with questions regarding socio-demographic characteristics, participants’ characteristics and motivational factors. The data were analyzed using descriptive and analytical statistics. Findings: The most important motivational factors are: salary, good interpersonal relationships and team work, contribution to population’s health and patient’s satisfaction. Around 10% of the participants thought that work could be done well even without motivational factors’ presence. Employees from the areas outside Belgrade rated job security higher in comparison with employees from Belgrade. A study conducted at the University of llorin Teaching Hospital in 2011 showed that salary was the most important motivational factor, followed by job security (Ojokuku& Salami, 2011). Contribution: Salary is an important motivational factor for employees in health care facilities in Serbia. Managers should work on the improvement of motivational factors through acknowledgement of needs of individual employees as well as through involving employees into decision making

The six-factor model of the SATS 36 (standardized parameter estimates).

<p>The six-factor model of the SATS 36 (standardized parameter estimates).</p

Validation and Cultural Adaptation of the Serbian Version of the Pediatric Outcome Data Collection Instrument (PODCI) in Children with Obstetrical Brachial Plexus Lesion

Background and objectives: Pediatric Outcome Data Collection Instrument (PODCI) is among the most described scales developed to evaluate the physical status of children and adolescents with various musculoskeletal disorders. We aimed to translate PODCI from English to Serbian, culturally adopt items and domains, evaluate the temporal stability, internal consistency and the test–retest reliability of PODCISR in children with obstetrical brachial plexus lesion (OBPL), and finally, to test the construct validity of PODCISR against muscular manual test (MMT) Materials and Methods: The study included 48 eligible participants aged between 2 and 10 years with OBPL. The MMT was used to test the construct validity. Results: There were no significant differences (p > 0.05) between test and retest for all PODCISR domains. Correlations for all tested domains with MMT were statistically significant except for biceps muscle and domains II and IV. Cronbach’s alpha value of the Global Functioning Scale was good and equaled 0.838 for test and 0.832 for retest session. Cronbach’s α was more than 0.600 for all PODCISR domains except for Domain II and for Domain IV. The observed Test–Retest ICC for all PODCISR domains scores ranged from 0.899 to 0.996. Conclusion: The Serbian version of PODCI (PODCISR) was successfully translated and transculturally adopted. It has satisfactory temporal stability, construct validity and test–retest reliability as well as relevant internal consistency

Regression models of variables associated with student attitudes towards statistics.

<p>*For n = 141 students; GPA = Grade Point Average.</p><p>Regression models of variables associated with student attitudes towards statistics.</p

Descriptive statistics of student attitudes towards statistics (n = 415).

<p>Descriptive statistics of student attitudes towards statistics (n = 415).</p

Correlations among the SATS components scores.

<p>Correlations among the SATS components scores.</p