Incomplete Induction Research Articles

Dynamics of SARS-CoV-2 immunity after vaccination and breakthrough infection in rituximab-treated rheumatoid arthritis patients: a prospective cohort study.

SARS-CoV-2 vaccination in rheumatoid arthritis (RA) patients treated with B cell-depleting drugs induced limited seroconversion but robust cellular response. We aimed to document specific T and B cell immunity in response to vaccine booster doses and breakthrough infection (BTI). We included 76 RA patients treated with rituximab who received up to four SARS-CoV-2 vaccine doses or three doses plus BTI, in addition to vaccinated healthy donors (HD) and control patients treated with tumor necrosis factor inhibitor (TNFi). We quantified anti-SARS-CoV-2 receptor-binding domain (RBD) Spike IgG, anti-nucleocapsid (NC) IgG, 92 circulating inflammatory proteins, Spike-binding B cells, and Spike-specific T cells along with comprehensive high-dimensional phenotyping and functional assays. The time since the last rituximab infusion, persistent inflammation, and age were associated with the anti-SARS-CoV-2 RBD IgG seroconversion. The vaccine-elicited serological response was accompanied by an incomplete induction of peripheral Spike-specific memory B cells but occurred independently of T cell responses. Vaccine- and BTI-elicited cellular immunity was similar between RA and HD ex vivo in terms of frequency or phenotype of Spike-specific cytotoxic T cells and in vitro in terms of the functionality and differentiation profile of Spike-specific T cells. SARS-CoV-2 vaccination in RA can induce persistent effector T-cell responses that are reactivated by BTI. Paused rituximab medication allowed serological responses after a booster dose (D4), especially in RA with lower inflammation, enabling efficient humoral and cellular immunity after BTI, and contributed overall to the development of potential durable immunity.

ԻՐԱՎԱԿԱՆ ԿԱՆԽԱՎԱՐԿԱԾՆԵՐԻ ԵՎ ՖԻԿՑԻԱՆԵՐԻ ԷՈՒԹՅԱՆ ԲԱՑԱՀԱՅՏՄԱՆ ՏԵՍԱԳՈՐԾՆԱԿԱՆ ՄՈՏԵՑՈՒՄՆԵՐԸ

For the emergence of legal consequences, in addition to real factual circumstances, legally permissible assumptions about factual circumstances - legal presumptions and fictions - are of great importance. Inadequate study of the characteristics and correlation of presumptions and fictions causes difficulties in law-making and law-enforcement practice. The difficulty in distinguishing these two phenomena is due to the fact that they are quite similar and closely related. The purpose of this article is to investigate the characteristics and correlation of legal fictions and presumptions. In order to achieve the set goal, the following main tasks were identified: ➢ to study the nature of legal presumptions and fictions, highlighting their commonalities and features, ➢ to study the relationship between legal presumptions and fictions, ➢ to develop of proposals aimed at fixing presumptions and fictions in legal acts and improving their application in practice. The subject of the study was examined with the use of general and special scientific methods, such as dogmatic, comparative legal, logical and legal modelling. As a result of the conducted research, a number of conclusions were made, the main contents of which are as follows: Legal presumption and fiction perform similar functions in the process of legal regulation. Their existence is due to the need to overcome the gaps in the legislation, to eliminate uncertainty in public relations. The meaning of the existence of legal fictions and presumptions is to create, with the help of an assumption, a legal consequence that would normally result from an event or action, they replace legal facts in the service of overcoming uncertainty. Fiction and presumption are beyond reality. They do not exist in the real world, but they are an integral part of the legal reality. At the same time, the analysis of their relationship has shown that, despite existing similarities, these normative generalizations are different. A presumption is rebuttable, and the assumption to be asserted is probable, while a fiction is irrefutable, and a proposition defined by a fiction is false. Presumption is inductive in nature, in the form of incomplete induction, and fiction is deductive. The purpose of using fiction is to recognize as true a assumption that is consciously inconsistent with reality, which does not pursue the goal of establishing the truth, its main purpose is to regulate those relations that cannot be regulated in any other way. Presumptions establish a necessary legal fact based on the probability of its existence. Based on the results of the research was proposed to supplement the Law of the Republic of Armenia on Normative Legal Acts with a new article on the use of legal presumptions and fictions. The proposed addition will have a guiding significance from the point of view of modeling legal norms. With that addition, it will be possible to subject the legislative and sub-legislative field to systematic and comprehensive regulation in terms of the application of legal presumptions and fictions.

الأحاديث العقدية الواردة في الحوار بعد البعثة النبوية المباركة جمعاً وتخريجاً ودراسةً

This research aims to collect Hadiths relevant to dialogue after the prophetic mission from its original sources, to extract some of the lessons obtained from them without delving into the jurisprudential details, comfine to valid Haiths from these honorable prophetic dialogues and preserving their majestic and venerable words, and focusing on clarifying the prophetic merits, noble morals, and the signs of mercy that characterized our Holy Prophet. The descriptive approach was adopted with its analytical and critical sides, and the incomplete induction approach was adopted to collect some appropriate data from selected Hadiths on the topic of dialogue. One of the important results and lessons of this research is that the person who has a dialogue with others, especially in the great matters in which the request to move from one religion to another, and from one doctrine to another, should make clear his great concern for him, his complete compassion for him, and his great desire for his salvation and safety. Another finding is the legality of dialogue with the infidels if it is for the purpose of calling them to the truth and guidance,or removing some of the suspicions that they have in their minds about our religion if it is done by someone who is qualified for that. Another finding is Da’wah needs patience and confidence and great knowledge about tradition and liguestic proverb and rhetoric.

Shari'a Governence in Sukuk Issuance

This paper examines the issue of Shariah governance in sukuk issuance by examining the parameters implemented. The problem the paper addresses is the conflicting views of scholars in determining the responsibility of the Shariah bodies towards their fatwas and resolutions related to the issuance of sukuk. The paper employs the incomplete induction methodology by extracting contemporary texts addressing the legal and Shariah status of the Shariah Supervisory Board and the nature of the contractual relationship with them. it also applies a critical comparative analysis that highlights the fundamentals the scholars' conflicting views, to adopt the most correct of them. The research concluded with a set of findings, among them the scholars' agreement in principle to make the Shariah body liable and bear legal responsibility either criminal or civil or both, if it contravened the Shariah provisions, however, they differed in the rules defining acts which are considered to be contrary to the Shariah provisions and the conditions to execute the punishments.

MM-257: It’s the Response That Matters: Real-World Data of Multiple Myeloma Patients Treated without Upfront Stem Cell Transplant

Context The treatment paradigm of newly diagnosed multiple myeloma (NDMM) has changed in the last decade. We report treatment outcomes among NDMM patients in the era of proteasome inhibitors (PI) and newer immunomodulatory drugs (IMiDs) in an Indian cohort who were not planned for upfront stem cell transplant. Objectives The primary objective was to determine the progression-free survival (PFS) of NDMM patients. Secondary objectives included objective response rates (ORR), (≥ partial response [PR]), and factors for relapse. Design Single-center ambispective study of NDMM patients diagnosed between January 2014 and December 2019 and followed until May 2021. Setting A North Indian tertiary cancer referral center. Patients Records of 650 NDMM patients were screened for the study. All received initial induction therapy followed by maintenance treatment. Two hundred forty-eight (39.2%) patients with incomplete induction therapy and significant missing data were excluded; 402 patients were included in study. Results Median age was 59.4 years (range: 23 to 84 years), and the male:female ratio was 1.9:1. Two hundred twenty-five (56%) patients had an IgG subtype, 248 (61.7%) patients had ISS stage III, 323 (80.3%) patients received triplet-based induction regimen, and 79 (19.7%) with doublets. VRd was the most common regimen, used in 123 (32.1%) patients. Following induction, 222 (52.2%) patients were treated with bortezomib, 142 (35.3%) received IMiDs, and 12% received no maintenance. ORR was 84.9% (67/79) with doublets and 95.2% (302/323) with triplets. Complete response was observed in 31.4% (103/323) patients on triplets and 29.1% (23/79) patients on doublets. After a median follow-up of 32.9 months (range: 0–102 months), median PFS did not differ by type of induction (22.8 vs 28.5 months in doublets; hazard ratio [HR] 1.06, 95% CI 0.71–1.58; p=0.8). Multivariate Cox proportion analysis suggested that response to induction ( Conclusion In NDMM patients, we suggest that depth of response, irrespective of induction and treatment with IMiDs, predicts a better PFS. However, these findings require validation by a randomized, controlled trial.

Multi-index Evaluation of Health Care System and Its Effect Prediction

Health care systems are crucial to people’s lives, so we established a quantitative model of multi-index health care assessment system to evaluate health care systems of different countries objectively. Firstly, we adopted the entropy weight method to calculate the weight of each indicator and built a linear function to derive the scoring results of the system in each country. Secondly, we used the incomplete induction method for the secondary screening of indicators, and the weight of selected seven indicators are: 0.16 0.11 0.13 0.14 0.19 0.15 0.12. Thirdly, we compared different countries’ health care systems. Compared to the America’s health care system, Japan had a better one, while China had a poorer one, and the scores of them are: 71.23 77.87 38.96. Finally, we proposed two suggestions to U.S. and predicted its improvement effects by BP neural network. Given the ease of implementation, cost and other issues, the latter is considered more appropriate.

Evaluation of Three Medetomidine-Based Anesthetic Protocols in Free-Ranging Wild Boars (Sus scrofa).

Three medetomidine-based drug protocols were compared by evaluating time courses, reliability and physiological effects in wild boars. A total of 21 cage-trapped wild boars (Sus scrofa) were immobilized using one of the following drug combinations; MTZ: medetomidine (0.2 mg/kg) + tiletamine-zolazepam (2.0 mg/kg), MK: medetomidine (0.15 mg/kg) + ketamine (5 mg/kg), and MKB: medetomidine (0.1 mg/kg) + ketamine (5.0 mg/kg) + butorphanol (0.2 mg/kg). Induction time, recovery time, and physiological variables were recorded and arterial blood gas analysis measured twice, before and after 15 min of oxygen supplementation (0.5–1.0 L/min). For reversal, 4 mg of atipamezole per mg of medetomidine was administered intramuscularly. The boars recovered in the cage and were released once ataxia resolved. The MK group had significantly longer recovery times (mean 164 min ± 79 SD) compared to the other groups. MKB elicited longer and incomplete induction compared to the other groups (mean induction time 20 min ± 10 SD), decreasing the efficiency of the capture and increasing the risk of hyperthermia. Both ketamine-based protocols required additional ketamine intramuscularly to prolong the anesthesia after 20–40 min from induction. Agreement between the pulse oximeter and the blood gas analyzer was low, with the pulse oximeter underestimating the real values of arterial oxyhemoglobin saturation, particularly at higher readings. Mild acute respiratory acidosis (PaCO2 45–60 mmHg) and mild to moderate hypoxemia (PaO2 69–80 mmHg) occurred in most boars, regardless of the treatment group but especially in the MKB group. The acid-base status improved and hypoxemia resolved in all boars during oxygen supplementation, with the PaO2 rising above the physiological reference range (81.6–107.7 mmHg) in many individuals. MK and MKB induced safe and reliable immobilization of wild boars for at least 20 min. Supplemental oxygen delivery is recommended in order to prevent hypoxemia in wild boars immobilized with the protocols used in the present study. Long and ataxic recoveries occurred in most animals, regardless of the protocol, but especially in the MKB group.

Incomplete posterior vitreous detachment despite vitrectomy with silicone oil tamponade

The fundamental step of a successful vitrectomy is posterior vitreous detachment induction; however, incomplete induction sometimes occurs. It may not be well seen barely by ophthalmoscopy examination, but emulsified silicone oil droplets act as the agent highlighting out the two natural retro-hyaloid spaces. The emulsified silicone oil droplets float according to gravity, but were entrapped over the pre-optic disc and the pre-macular bursa, giving the funny double inverse hypopyon-like pattern over the posterior segment.

Identification of Values Shaping Inter-Organizational Relations on the Example of the Project The Metropolitan Theatres Night

Inter-organizational cooperation is based on the development of relationships between partners who have attractive tangible or intangible values which may be the subject of exchange. In inter-organizatio-nal cooperation, at least two key stages of relationship development can be distinguished. The first con-cern is initiating ties between potential partners; the second, strengthening, expanding and deepening these ties. The authors attempted to identify the values that affect the relations between organizations cooperating on a joint project in the cultural sphere. The research process was based on the assump-tions of grounded theory. The incomplete induction method was used. In order to solve this research problem, the authors analysed a case study of a network project led by the Górnośląsko-Zagłębiowska Metropolis, entitled Metropolitan Theatres Night, and in addition, conducted qualitative research (in-dividual in-depth interviews and written surveys), amongst organizations cooperating on this project. The research proved that the assessment of key values to project partners at the stage of initiating and developing cooperation is varied. At the stage of initiating relations, the financial benefits of coopera-tion and the prestige associated with it are most important. In contrast, at the stage of cooperation development financial benefits come first, while other elements are of secondary importance. The rese-arch results show that the partnership does not use many opportunities resulting from the synergy of resources or joint learning during the long period of cooperation. In connection with the above, the authors defined recommendations that may serve to improve inter-organizational cooperation in this type of project and in other partnerships.

Suppression of MKL1 promotes adipocytic differentiation and reduces the proliferation of myxoid liposarcoma cells.

Myxoid liposarcoma (MLS) is thought to occur due to defective adipocytic differentiation in mesenchymal stem cells. A promising strategy for MLS treatment is the prevention of sarcomagenesis by promoting the terminal differentiation of MLS cells into adipocytes. Previous studies have reported that the suppression of megakaryoblastic leukemia 1 (MKL1) expression induces adipocytic differentiation in preadipocyte cell lines. The present study aimed to investigate the effects of MKL1 suppression on MLS cells. In the present study, MKL1 knockdown was demonstrated to promote the adipocytic differentiation of an MLS-derived cell line, designated 1955/91, under adipogenic conditions. This suggests that therapeutic targeting of the MKL1-associated molecular pathway has potential as a promising method of MLS treatment. However, the induction of adipogenesis by MKL knockdown was incomplete, and Oil Red O staining indicated that intracellular lipid droplets were only sporadically generated. Conversely, MKL1 knockdown reduced the growth of the MLS cells. As adipocytic differentiation in vitro requires cellular confluence, the decreased growth rate of the MLS cells following MKL1 knockdown could be attributed to the incomplete induction of adipogenesis. Translocated in liposarcoma-CCAAT/enhancer-binding protein homologous protein (TLS-CHOP) is an MLS-specific oncoprotein that is thought to play key roles in sarcomagenesis and the suppression of adipocytic differentiation. However, the results of western blotting analyses suggest that TLS-CHOP has limited effects on MKL1 expression in MLS cells and that MKL1 knockdown hardly affects TLS-CHOP expression. Thus, it is postulated that the inhibitory effect of TLS-CHOP on adipogenesis is not associated with MKL1 expression. However, MKL1 and the molecular pathway involving MKL1 appear to be attractive targets for the differentiation therapy of MLS.

In Pursuance of Differentiation Inducers to Combat Cancer via Targeting of Abnormal Methylation Enzymes

Cell differentiation agent-2 (CDA-2) was a promising hypomethylating agent approved by the Chinese FDA for the therapy of MDS in China. The active components of CDA-2 are differentiation inducers (DIs) and differentiation helper inducers (DHIs). DIs are chemicals capable of eliminating telomerase from abnormal MEs commonly found in human cancers. The major DI of CDA-2 is an organic acid without UV absorption. Without UV absorption as a guide, it was difficult to purify the DI of CDA-2 for identification. Thus, we pursued possible candidates to function as DIs in this study.
 Cancer MEs become abnormal due to association with telomerase. Naturally we sought telomerase inhibitors as possible candidates of DIs. Prostaglandin E2 (PGE2) attracted our attention because it was implicated to involve in wound healing, which is a major biological mission of progenitor stem cells (PSCs) and cancer stem cells (CSCs). Eradication of CSCs has been a major focus of our studies. Besides, PGE2 fits the description of the major DI of CDA-2.
 Induction of terminal differentiation (TD) of HL-60 cells by NBT assay was employed to evaluate the activity of chemicals as DIs. Cell growth was based on cell numbers. All-trans retinoic acid (ATRA) and 12-O-tetradecanoylphorbol-13-acetate (TPA) are two well known DIs. ATRA displayed a wide active dosage range from 0.2 to 4.5 µM with a maximum of inducing 89% NBT+ cells at 3 µM. TPA displayed a narrow active dosage range from 0.2 to 0.6 nM with a maximum of inducing 84% NBT+ cells at 0.4 nM. BIBR1532 and bodine were the two telomerase inhibitors studied. Both were found active as DIs. BIBR1532 was active in the dosage range from 30 to 75 µM with a maximum of inducing 86% at 63 µM. Bodine was active in the dosage range from 60 to 98 µM with a maximum of inducing 80% at 98 µM. PGE2 was active in the dosage range from 20 to 70 µM with a maximum of inducing 80% at 56 µM.
 DIs at dosages not active as DIs could function as effective DHIs to other DIs. RI0.5 of BIBR1532, boldine and PGE2 as DHIs were 2.02 µM, 3.11 µM, and 0.92 µM, respectively.
 DIs alone, no matter how effective, could not induce NBT+ cells to reach 100%. 95% (89% plus 6% of blank) was the highest value achieved by ATRA. Incomplete induction of TD was the reason for frequent recurrence when ATRA was used alone in the therapy of acute promyelocytic leukemia (APL). A combination of ATRA and a DHI could induce NBT+ cells to reach 100% to avoid recurrence.

Hypereosinophilia as a Presenting Symptom of Acute Lymphoblastic Leukemia in a Child

Hypereosinophilia is rare in children and represents primary or secondary conditions, the latter of which is associated with other diseases (parasitic infections and allergic, autoimmune, and neoplastic diseases). In small number of cases (< 1%) it is a part of the clinical presentation of acute lymphoblastic leukemia, the most common malignancy in children. More often hypereosinophilia precedes the symptoms of leukemia and hinders timely diagnosis, exposing patients in a high risk. In this report, a case of a child with acute lymphoblastic leukemia and hypereosinophilia is presented. The patient is a 30-month-old female, whose leukemia is preceded 2 weeks after hypereosinophilia. This symptom made the exact and timely diagnosis of oncological disease difficult. The further course of the disease was standard despite of delayed diagnosis and incomplete induction treatment due to the hepatic chemotoxicity. We present this case due to the rarity of hypereosinophilia in pediatric acute lymphoblastic leukemia. Every experience with such cases would be very useful for the improvement of the diagnosis of these patients. Moreover in our patient we did not find typical cytogenetic or molecular genetic abnormalities for this type of leukemia, and did not observe any clinical signs of organ complications specific for hypereosinophilia. Int J Clin Pediatr. 2020;9(2):59-63 doi: https://doi.org/10.14740/ijcp365

ХУДОЖНЬО-ОБРАЗНІ ОСОБЛИВОСТІ СПЕЦОДЯГУ В ДИЗАЙНІ ХХ СТОЛІТТЯ

Analysis and generalization of scientific and practical developments in the aesthetic-harmonic design of special-purpose clothing: features of forming and means of compositional expressiveness. For the analysis of literary sources of information, the literary-analytical method was used; for the analysis of visual sources - the visual-analytical method. The method of deduction (conclusions about the process of forming uniforms for workers of coal and mining mines) and incomplete induction (manifestations of compositional expression) were used. The practical developments and conceptual provisions of the activity of constructivist artists in the creation of clothes for labor are considered. The situation in the field of designing overalls in the territory of the Ukrainian SSR and the USSR as a whole has been investigated. The characteristic of changes in the form of overalls, intended for workers of coal mining and mining mines during 1920-1980 years was received. The overalls are considered as an art object and analyzed the manifestations of possible means of compositional expressiveness, the principles of combining forms in suits of various special purpose. The means of compositional expressiveness and the volume-spatial form of special purpose clothes from the position of visual perception are systematized. The modification of the form of overalls made during the 1920-1980 years for workers of coal mining and mining mines during the period was investigated. The obtained results of the research give an opportunity to form an idea of the aesthetic component in the general concept of special purpose clothes and to supplement the available theoretical information in this field. Also, the findings of the study may serve as an additional informative source at the stage of artistic-constructive analysis in modern design engineering not only the class of industrial clothing, but also domestic.

Successful Salvages of Partially Covered Esophageal Metal Stent Using Repeated Sessions of Argon Plasma Coagulation

Esophageal stents have utility in temporizing esophageal leaks and benign or malignant strictures, but their removal can be complicated by tissue embedment. Special methods for removal include argon plasma coagulation (APC) induction of tissue necrosis and stent-in-stent technique (SIS). APC is a non-contact thermal technology that uses argon gas to deliver plasma of thermal energy to an area adjacent to the probe, and it is widely used as a method to control bleeding. APC can be set at a precise setting to limit necrosis to the superficial layer of the esophageal mucosa. On the other hand, SIS utilizes a second esophageal stent that is placed within the first stent to induce necrosis of embedded tissue, enabling removal of both stents. We present two cases with successful removal of embedded, partially-covered self-expandable esophageal metal stents (SEMS) using APC at a precise setting of 50W. One case showed the flexibility of APC in removal of a migrated SEMS in a 75-year-old female patient with metastatic esophageal cancer. The stent had migrated into the stomach with the distal tip eroding into gastric mucosa with embedment of proximal stent into distal esophagus. Given the positioning, SIS was not possible. APC was used to induce necrosis of embedded tissue. Two days later, repeat APC treatment was performed with removal of the stent with grasping forceps<./p> The second case demonstrated the efficacy of APC in removal of a SEMS placed for an esophageal leak after sleeve gastrectomy in a 44-year-old female patient. A partially-covered SEMS was chosen to minimize migration. After esophageal leak resolution one month later, APC was used to induce tissue necrosis of areas of stent embedment. On repeat endoscopy, the esophageal stent was easily dislodged using blunt dissection with a plastic cap with minimal bleeding. We propose that APC is a superior technique for esophageal stent removal compared to the SIS. APC is more readily available with decreased cost compared to the SIS which requires a second stent. Placing a stent within another can be complicated by incomplete induction of necrosis, severe pain and tracheal compression. APC and SIS both require at least two separate days of endoscopy, but APC in our study has only needed an interval time of 2-4 days versus median time of 9-14 days for SIS. Given the small sample sizes, further investigation is needed to determine the optimal technique for esophageal stent removal.2115_A Figure 1. CT Scan of Abdomen showing esophageal stent migration with erosion into gastric fundus.2115_B Figure 2. #1 shows the migrated esophageal stent. #2 Induction of tissue necrosis with APC.

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes. This retrospective cohort study included 92 NS patients from BC Children's Hospital (1990-2010). We excluded secondary causes of NS, age < 1year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid-sparing agent (SSA). Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000mg/m2 respectively. Doses ≤ 2000mg/m2 showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175days), and higher SSA use (36 vs 14%) compared to higher doses. Doses ≤ 2500mg/m2 also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in ≤ 3000 vs > 3000mg/m2 doses. Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500mg/m2. Further prospective studies are warranted.

Differentiation of adipose-derived stem cells into Schwann cell-like cells through intermittent induction: potential advantage of cellular transient memory function

BackgroundPeripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden. Autologous nerve grafting, the gold standard treatment for peripheral nerve defects, still has a number of technical limitations. Tissue engineering technology is a novel therapeutic strategy, and mesenchymal stromal cells (MSCs) are promising seed cells for nerve tissue engineering. However, the efficiency of traditional methods for inducing the differentiation of MSCs to Schwann cell-like cells (SCLCs) remains unsatisfactory.MethodsHere, we propose an intermittent induction method with alternate use of complete and incomplete induction medium to induce differentiation of adipose-derived stem cells (ASCs) to SCLCs. The time dependence of traditional induction methods and the efficiency of the intermittent induction method and traditional induction methods were evaluated and compared using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and co-culture with the dorsal root ganglion (DRG) in vitro. Cell transplantation was used to compare the effects of the traditional induction method and the intermittent induction method in repairing sciatic nerve defects in vivo.ResultsThe results of the present study indicated that the intermittent induction method is more efficient than traditional methods for inducing ASCs to differentiate into SCLCs. In addition, SCLCs induced by this method were closer to mature myelinating Schwann cells and were capable of secreting neurotrophins and promoting DRG axon regeneration in vitro. Furthermore, SCLCs induced by the intermittent induction method could repair sciatic nerve defects in rats by cell transplantation in vivo more effectively than those produced by traditional methods.ConclusionIntermittent induction represents a novel strategy for obtaining seed cells for use in nerve tissue engineering.

Procedury naukowe indukcji zupełnej i niezupełnej w metodologii nauk o zarządzaniu

The article presents the characteristics of the two basic scientific procedures used in management science. The procedures for complete induction and incomplete induction are presented from the perspective of the general methodology of science, the philosophy of science and the achievements of the methodology of management science. The analysis of these procedures specifically focuses on methods and techniques as well as on methodological directives relating them to the distinguished phases within the procedures of scientific research.

The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18.

The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon - closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support.

Ethical Media Content Adjustment between Croatian and European Union Regulations – Following Local Elections 2013 in Lika-senj County

Mass media in Croatian media space is generally defined according to profitability and is based on the definition of mass media as industrial and commercial organisation that does not produce and distribute information but goods; in that situation hidden advertising appears in terms of income decreasing ( especially during political campaigns); that kind of situation is in direct contradiction with media freedom as crucial pre-condition of ethical principles achievement. On the example of the analysis of media content published in electronic and printed media during the campaign carried out in 2013. – local elections in Lika-senj county, this work will show how complex are ethical doubts that journalists meet in open societies in which media freedom is very large; point out the proportion and examples of ethical standards violation and destabilisation of the border between good and bad taste by violation of privacy, augment of information damage by unfair reporting, and publisher or interest groups pressure which results in placing incomplete, subjective, biased or incorrect information to the public. The aim of this work is to (by methods of incomplete induction, deduction, description, analysis and sample method) indicate on insufficient balance of media content between Croatian and European Union regulatives, the lack of critical public opinion in media reporting and insufficient adopted freedom and responsibilities in media content creation.

Small‐molecule modulators of Nkx6.1 expression in pancreatic progenitor cells during directed differentiation of human embryonic stem cell to insulin producing beta cells

Type 1 diabetes is characterized by destruction of the insulin‐producing pancreatic beta cells, resulting in dysregulation of blood glucose levels. As such, the identification of small‐molecules capable of efficiently inducing the differentiation of human embryonic stem cells (hESC) to insulin producing beta cells may provide a route to cell transplantation therapies for these patients. In 2012, several protocols were reported to generate pancreatic precursor cells capable of further differentiation into beta cells when transplanted into mice. However, these pancreatic precursors do not generate functional beta cells in vitro. One possible explanation of this effect is the absence of the critical pancreatic progenitor transcription factor, Nkx6.1, in over 60% of the hESC derived pancreatic progenitor cells in vitro. Thus incomplete induction of Nkx6.1 may represent a barrier to beta cell production in vitro. To this end, we sought to uniformly induce Nkx6.1 expression in pancreatic progenitors. Herein, we report the development of a combinatorial screening platform for the identification of small‐molecules that can induce Nkx6.1 expression in pancreatic precursor cells, and the elucidation of pathways driving this aspect of beta cell differentiation.