Detection and Localization of Small Moving Objects in the Presence of Sensor and Platform Movement.

In this paper, we address the challenge of detecting small moving targets in dynamic environments characterized by the concurrent movement of both platform and sensor. In such cases, simple image-based frame registration and optical flow analysis cannot be used to detect moving targets. To tackle this, it is necessary to use sensor and platform meta-data in addition to image analysis for temporal and spatial anomaly detection. To this end, we investigate techniques that utilize inertial data to enhance frame-to-frame registration, consistently yielding improved detection outcomes when compared against purely feature-based techniques. For cases where image registration is not possible even with metadata, we propose single-frame spatial anomaly detection and then estimate the range to the target using the platform velocity. The behavior of the estimated range over time helps us to discern targets from clutter. Finally, we show that a KNN classifier can be used to further reduce the false alarm rate without a significant reduction in detection performance. The proposed strategies offer a robust solution for the detection of moving targets in dynamically challenging settings.

Satisfaction of patients in government medical teaching institutes of Peshawar Khyber Pakhtunkhwa, Pakistan: a cross-sectional analytical study.

Objective: To evaluate patient satisfaction and its associated factors in teaching hospitals. METHODS: The cross-sectional, analytical study was conducted from September to December 2022 at three publicsector medical teaching hospitals in Peshawar, Pakistan, and comprised adult patients of either admitted to various hospital wards for at least 2 days. Data was collected using a predesigned a closed-ended questionnaire assessing patient satisfaction in different domains like, facilitation at the admission, professional knowledge and skills of the attending doctors, quality of diagnostic and nursing services, and basic amenities. Data was analysed using SPSS version origin Pro 2022a. RESULTS: There were 473 patients with a male-female ratio of 3:1, with mean age 43.3+14.7 years (range: 11-85 years), and mean hospital stay 5.96+3.37 days (range: 2-18 days). Of the 2,365 response statements for facilitation at the admission counter, 2,051(87%) were positive; of the 2,365 statements for attending doctors, 2,012(85%) were positive; of the 2,838 statements for nursing care, 2,122(75%) were positive; of 946 statements for diagnostic services, 627(66%) were positive; and of the 3,311 statements for basic amenities at the hospital, 1,246(38%) were positive. Overall, of the 11,825 response statements, 8058(68%) were positive. The patient satisfaction was significantly co-related with education and hospital stay (p<0.05). Conclusion: Patients were found to be generally satisfied with healthcare services, but not with the provision of basic amenities.

Fidelity Assessment of Motion Platform Cueing: Comparison of Driving Behavior under Various Motion Levels.

The present paper focuses on vehicle simulator fidelity, particularly the effect of motion cues intensity on driver performance. The 6-DOF motion platform was used in the experiment; however, we mainly focused on one characteristic of driving behavior. The braking performance of 24 participants in a car simulator was recorded and analyzed. The experiment scenario was composed of acceleration to 120 km/h followed by smooth deceleration to a stop line with prior warning signs at distances of 240, 160, and 80 m to the finish line. To assess the effect of the motion cues, each driver performed the run three times with different motion platform settings-no motion, moderate motion, and maximal possible response and range. The results from the driving simulator were compared with data acquired in an equivalent driving scenario performed in real conditions on a polygon track and taken as reference data. The driving simulator and real car accelerations were recorded using the Xsens MTi-G sensor. The outcomes confirmed the hypothesis that driving with a higher level of motion cues in the driving simulator brought more natural braking behavior of the experimental drivers, better correlated with the real car driving test data, although exceptions were found.

Automated indexing using NLM's Medical Text Indexer (MTI) compared to human indexing in Medline: a pilot study.

Objective: In 2002, the National Library of Medicine (NLM) introduced semi-automated indexing of Medline using the Medical Text Indexer (MTI). In 2021, NLM announced that it would fully automate its indexing in Medline with an improved MTI by mid-2022. This pilot study examines indexing using a sample of records in Medline from 2000, and how an early, public version of MTI's outputs compares to records created by human indexers. Methods: This pilot study examines twenty Medline records from 2000, a year before the MTI was introduced as a MeSH term recommender. We identified twenty higher- and lower-impact biomedical journals based on Journal Impact Factor (JIF) and examined the indexing of papers by feeding their PubMed records into the Interactive MTI tool. Results: In the sample, we found key differences between automated and human-indexed Medline records: MTI assigned more terms and used them more accurately for citations in the higher JIF group, and MTI tended to rank the Male check tag more highly than the Female check tag and to omit Aged check tags. Sometimes MTI chose more specific terms than human indexers but was inconsistent in applying specificity principles. Conclusion: NLM's transition to fully automated indexing of the biomedical literature could introduce or perpetuate inconsistencies and biases in Medline. Librarians and searchers should assess changes to index terms, and their impact on PubMed's mapping features for a range of topics. Future research should evaluate automated indexing as it pertains to finding clinical information effectively, and in performing systematic searches.

Schizosaccharomyces pombe Ppr10 and Mpa1 together mediate mitochondrial translational initiation.

Pentatricopeptide repeat (PPR) proteins are a large family of proteins that act primarily at different posttranscriptional steps of organellar gene expression. We have previously found that the Schizosaccharomyces pombe PPR protein mpal10 interacts with mitochondrial translational activator Mpa1, and both are essential for mitochondrial protein synthesis. However, it is unclear how these two proteins function in mitochondrial protein synthesis in S. pombe. In this study, we further investigated the role of Ppr10 and Mpa1 in mitochondrial protein synthesis. Mitochondrial translational initiation requires two initiation factors, Mti2 and Mti3, which bind to the small subunit of the mitochondrial ribosome (mt-SSU) during the formation of the mitochondrial translational initiation complex. Using sucrose gradient sedimentation analysis, we found that disruption of ppr10, mpa1, or the PPR motifs in Ppr10 impairs the association of Mti2 and Mti3 with the mt-SSU, suggesting that both Ppr10 and Mpa1 may be required for the interaction of Mti2 and Mti3 with the mt-SSU during the assembly of mitochondrial translational initiation complex. Loss of Ppr10 perturbs the association of mitochondrially encoded cytochrome b (cob1) and cytochrome c oxidase subunit 1 (cox1) mRNAs with assembled mitochondrial ribosomes. Proteomic analysis revealed that a fraction of Ppr10 and Mpa1 copurified with a subset of mitoribosomal proteins. The PPR motifs of Ppr10 are necessary for its interaction with Mpa1 and that disruption of these PPR motifs impairs mitochondrial protein synthesis. Our results suggest that Ppr10 and Mpa1 function together to mediate mitochondrial translational initiation.

How mycobacterium tuberculosis infection could lead to the increasing risks of chronic fatigue syndrome and the potential immunological effects: a population-based retrospective cohort study.

BACKGROUND: Chronic fatigue syndrome (CFS) has been shown to be associated with infections. Tuberculosis (TB) is a highly prevalent infectious disease. Patients with chronic fatigue syndrome and post-tuberculosis experience similar symptoms. Furthermore, chronic fatigue syndrome and tuberculosis share similar plasma immunosignatures. This study aimed to clarify the risk of chronic fatigue syndrome following the diagnosis of Mycobacterium tuberculosis infection (MTI), by analyzing the National Health Insurance Research Database of Taiwan. METHODS: 7666 patients aged 20 years or older with newly diagnosed Mycobacterium tuberculosis infection during 2000-2011 and 30,663 participants without Mycobacterium tuberculosis infection were identified. Both groups were followed up until the diagnoses of chronic fatigue syndrome were made at the end of 2011. RESULTS: The relationship between Mycobacterium tuberculosis infection and the subsequent risk of chronic fatigue syndrome was estimated through Cox proportional hazards regression analysis, with the incidence density rates being 3.04 and 3.69 per 1000 person-years among the non-Mycobacterium tuberculosis infection and Mycobacterium tuberculosis infection populations, respectively (adjusted hazard ratio [HR] = 1.23, with 95% confidence interval [CI] 1.03-1.47). In the stratified analysis, the Mycobacterium tuberculosis infection group were consistently associated with a higher risk of chronic fatigue syndrome in the male sex (HR = 1.27, 95% CI 1.02-1.58) and age group of ≥ 65 years old (HR = 2.50, 95% CI 1.86-3.38). CONCLUSIONS: The data from this population-based retrospective cohort study revealed that Mycobacterium tuberculosis infection is associated with an elevated risk of subsequent chronic fatigue syndrome.

MicroRNAs in Leukemias: A Clinically Annotated Compendium.

Leukemias are a group of malignancies of the blood and bone marrow. Multiple types of leukemia are known, however reliable treatments have not been developed for most leukemia types. Furthermore, even relatively reliable treatments can result in relapses. MicroRNAs (miRNAs) are a class of short, noncoding RNAs responsible for epigenetic regulation of gene expression and have been proposed as a source of potential novel therapeutic targets for leukemias. In order to identify central miRNAs for leukemia, we conducted data synthesis using two databases: miRTarBase and DISNOR. A total of 137 unique miRNAs associated with 16 types of leukemia were retrieved from miRTarBase and 86 protein-coding genes associated with leukemia were retrieved from the DISNOR database. Based on these data, we formed a visual network of 248 miRNA-target interactions (MTI) between leukemia-associated genes and miRNAs associated with ≥4 leukemia types. We then manually reviewed the literature describing these 248 MTIs for interactions identified in leukemia studies. This manually curated data was then used to visualize a network of 64 MTIs identified in leukemia patients, cell lines and animal models. We also formed a visual network of miRNA-leukemia associations. Finally, we compiled leukemia clinical trials from the ClinicalTrials database. miRNAs with the highest number of MTIs were miR-125b-5p, miR-155-5p, miR-181a-5p and miR-19a-3p, while target genes with the highest number of MTIs were TP53, BCL2, KIT, ATM, RUNX1 and ABL1. The analysis of 248 MTIs revealed a large, highly interconnected network. Additionally, a large MTI subnetwork was present in the network visualized from manually reviewed data. The interconnectedness of the MTI subnetwork suggests that certain miRNAs represent central disease molecules for multiple leukemia types. Additional studies on miRNAs, their target genes and associated biological pathways are required to elucidate the therapeutic potential of miRNAs in leukemia.

Identification of a novel gene controlling homothallism in the yeast Kazachstania naganishii isolated in Japan.

A novel gene controlling homothallic life cycle was identified in the yeast Kazachstania naganishii isolated in Japan. This gene was isolated by means of complementing a mutation, mti1, which had led to heterothallism from original homothallism in the yeast. The configuration of original mutation in MTI1 gene revealed that a truncated product is formed due to occurrence of a stop codon by a nucleotide insertion. When the gene was disrupted with a marker, the disruptant spore clone was haploid and stably heterothallic. Disfunction of the gene caused inability to self-diploidize due to defect of mating-type interconversion. The gene MTI1 (for Mating Type Interconversion) is a weak homolog of the Saccharomyces cerevisiae VID22/ENV11, which has been reported to function in vacuolar protein processing. K. naganishii has a gene representing significant homology with the HO gene of S. cerevisiae on chromosome V, which has not been clarified to be involved in regulation of life cycle in K. naganishii. The MTI1 gene defined in this study is located on K. naganishii chromosome IV and does not represent significant homology to the above ScHO-like gene and any other genes concerning life cycles of yeasts. From the viewpoint of gene evolution, it is extremely interesting that the MTI1 gene is a new type of gene controlling homothallism in addition to an HO-type gene, leading to discovery of an unknown mechanism regulating life cycles in yeasts.

A small nuclear acidic protein (MTI-II, Zn2+-binding protein, parathymosin) attenuates TNF-α inhibition of BMP-induced osteogenesis by enhancing accessibility of the Smad4-NF-κB p65 complex to Smad binding element.

Pro-inflammatory cytokines prevent bone regeneration in vivo and activation of nuclear factor-κB (NF-κB) signaling has been proposed to lead to suppression of bone morphogenetic protein (BMP)-induced osteogenesis via direct binding of p65 to Smad4 in vitro. Application of a small nuclear acidic protein (MTI-II) and its delivered peptide, MPAID (MTI-II peptide anti-inflammatory drug) has been described to elicit therapeutic potential via strong anti-inflammatory action following the physical association of MTI-II and MPAID with p65. However, it is unclear whether MTI-II attenuates tumor necrosis factor (TNF)-α inhibition of BMP-induced osteogenesis. Herein, we found that TNF-α-mediated suppression of responses associated with BMP4-induced osteogenesis, including expression of the osteocalcin encoding gene Ocn, Smad binding element (SBE)-dependent luciferase activity, alkaline phosphatase activity, and alizarin red S staining were largely restored by MTI-II and MPAID in MC3T3-E1 cells. Mechanistically, MTI-II and MPAID did not inhibit nuclear translocation of p65 or disassociate Smad4 from p65. Further, results from chromatin immunoprecipitation (ChIP) analyses revealed that Smad4 enrichment in cells over-expressing MTI-II and treated with TNF-α was equivalent to that in cells without TNF-α treatment. Alternatively, Smad4 enrichment was considerably decreased following TNF-α treatment in control cells. Moreover, p65 enrichment in the Id-1 promoter SBE was detected only when cells over-expressing MTI-II were stimulated with TNF-α. Overall, our study concludes that MTI-II restored TNF-α-inhibited suppression of BMP-Smad-induced osteogenic differentiation by enhancing accessibility of the Smad4-p65 complex to the SBE rather than by liberating Smad4 from p65.

Prospects of Gene Knockouts in the Functional Study of MAMP-Triggered Immunity: A Review.

Plants depend on both preformed and inducible defence responses to defend themselves against biotic stresses stemming from pathogen attacks. In this regard, plants perceive pathogenic threats from the environment through pattern recognition receptors (PRRs) that recognise microbe-associated molecular patterns (MAMPs), and so induce plant defence responses against invading pathogens. Close to thirty PRR proteins have been identified in plants, however, the molecular mechanisms underlying MAMP perception by these receptors/receptor complexes are not fully understood. As such, knockout (KO) of genes that code for PRRs and co-receptors/defence-associated proteins is a valuable tool to study plant immunity. The loss of gene activity often causes changes in the phenotype of the model plant, allowing in vivo studies of gene function and associated biological mechanisms. Here, we review the functions of selected PRRs, brassinosteroid insensitive 1 (BRI1) associated receptor kinase 1 (BAK1) and other associated defence proteins that have been identified in plants, and also outline KO lines generated by T-DNA insertional mutagenesis as well as the effect on MAMP perception-and triggered immunity (MTI). In addition, we further review the role of membrane raft domains in flg22-induced MTI in Arabidopsis, due to the vital role in the activation of several proteins that are part of the membrane raft domain theory in this regard.

Women with extreme low AMH values could have in vitro fertilization success.

Circulating anti-müllerian hormone (AMH) and antral follicle count (AFC) are the best predictors of IVF outcomes. However, in extreme low AMH range especially for young patients, AMH prediction power loose its specificity to give real idea of pregnancy chance with IVF treatments and good prognosis of an extremely reduced ovarian reserve and expected poor response. Indeed, this retrospective study was conducted to evaluate IVF outcomes in patients following IVF-ICSI program with extremely low AMH levels (≤0.4 ng/ml; n = 390) compared to those presenting normal AMH range (1.3-2.6 ng/ml; n = 352) considered as control group. As expected, number of oocytes retrieved per patient, and embryological outcomes were significantly lower in the extremely low AMH levels group compared to control. Moreover, it was same trend concerning clinical outcomes but we have to note that even in extreme low AMH, patients could reach ineligible satisfying clinical pregnancy rate compared to control (17% vs 41%). For patients younger than 35 years, clinical pregnancy rate improved to 27%. Women with extreme low AMH values and especially younger ones, still have reasonable chances of achieving pregnancy, highlighting the default view of this category generally excluded from IVF program.

Clinical utility of arterial spin labeling imaging in disorders of the nervous system.

Neuroimaging is an indispensable tool in the workup and management of patients with neurological disorders. Arterial spin labeling (ASL) is an imaging modality that permits the examination of blood flow and perfusion without the need for contrast injection. Noninvasive in nature, ASL provides a feasible alternative to existing vascular imaging techniques, including angiography and perfusion imaging. While promising, ASL has yet to be fully incorporated into the diagnosis and management of neurological disorders. This article presents a review of the most recent literature on ASL, with a special focus on its use in moyamoya disease, brain neoplasms, seizures, and migraines and a commentary on recent advances in ASL that make the imaging technique more attractive as a clinically useful tool.

Vascular architecture mapping for early detection of glioblastoma recurrence.

OBJECTIVE: Treatment failure and inevitable tumor recurrence are the main reasons for the poor prognosis of glioblastoma (GB). Gross-total resection at repeat craniotomy for GB recurrence improves patient overall survival but requires early and reliable detection. It is known, however, that even advanced MRI approaches have limited diagnostic performance for distinguishing tumor progression from pseudoprogression. The novel MRI technique of vascular architectural mapping (VAM) provides deeper insight into tumor microvascularity and neovascularization. In this study the authors evaluated the usefulness of VAM for the monitoring of GB patients and quantitatively analyzed the features of neovascularization of early- and progressed-stage GB recurrence. METHODS: In total, a group of 115 GB patients who received overall 374 follow-up MRI examinations after standard treatment were retrospectively evaluated in this study. The clinical routine MRI (cMRI) protocol at 3 Tesla was extended with the authors' experimental VAM approach, requiring 2 minutes of extra time for data acquisition. Custom-made MATLAB software was used for calculation of imaging biomarker maps of macrovascular perfusion from perfusion cMRI as well as of microvascular perfusion and architecture from VAM data. Additionally, cMRI data were analyzed by two board-certified radiologists in consensus. Statistical procedures included receiver operating characteristic (ROC) analysis to determine diagnostic performances for GB recurrence detection. RESULTS: Overall, cMRI showed GB recurrence in 89 patients, and in 28 of these patients recurrence was detected earlier with VAM data, by 1 (20 patients) or 2 (8 patients) follow-up examinations, than with cMRI data. The mean time difference between recurrence detection with VAM and cMRI data was 147 days. During this time period the mean tumor volume increased significantly (p < 0.001) from 9.7 to 26.8 cm3. Quantitative analysis of imaging biomarkers demonstrated microvascular but no macrovascular hyperperfusion in early GB recurrence. Therefore, ROC analysis revealed superior diagnostic performance for VAM compared with cMRI. CONCLUSIONS: This study demonstrated that the targeted assessment of microvascular features using the VAM technique provided valuable information about early neovascularization activity in recurrent GB that is complementary to perfusion cMRI and may be helpful for earlier and more precise monitoring of patients suffering from GB. This VAM approach is compatible with existing cMRI protocols. Prospective clinical trials are necessary to investigate the clinical usefulness and potential benefit of increased overall survival with the use of VAM in patients with recurrent GB.

Phytophthora infestans RXLR effector SFI5 requires association with calmodulin for PTI/MTI suppressing activity.

Pathogens secrete effector proteins to interfere with plant innate immunity, in which Ca2+ /calmodulin (CaM) signalling plays key roles. Thus far, few effectors have been identified that directly interact with CaM for defence suppression. Here, we report that SFI5, an RXLR effector from Phytophthora infestans, suppresses microbe-associated molecular pattern (MAMP)-triggered immunity (MTI) by interacting with host CaMs. We predicted the CaM-binding site in SFI5 using in silico analysis. The interaction between SFI5 and CaM was tested by both in vitro and in vivo assays. MTI suppression by SFI5 and truncated variants were performed in a tomato protoplast system. We found that both the predicted CaM-binding site and the full-length SFI5 protein interact with CaM in the presence of Ca2+ . MTI responses, such as FRK1 upregulation, reactive oxygen species accumulation, and mitogen-activated protein kinase activation were suppressed by truncated SFI5 proteins containing the C-terminal CaM-binding site but not by those without it. The plasma membrane localization of SFI5 and its ability to enhance infection were also perturbed by loss of the CaM-binding site. We conclude that CaM-binding is required for localization and activity of SFI5. We propose that SFI5 suppresses plant immunity by interfering with immune signalling components after activation by CaMs.

Indispensable Role of Proteases in Plant Innate Immunity.

Plant defense is achieved mainly through the induction of microbe-associated molecular patterns (MAMP)-triggered immunity (MTI), effector-triggered immunity (ETI), systemic acquired resistance (SAR), induced systemic resistance (ISR), and RNA silencing. Plant immunity is a highly complex phenomenon with its own unique features that have emerged as a result of the arms race between plants and pathogens. However, the regulation of these processes is the same for all living organisms, including plants, and is controlled by proteases. Different families of plant proteases are involved in every type of immunity: some of the proteases that are covered in this review participate in MTI, affecting stomatal closure and callose deposition. A large number of proteases act in the apoplast, contributing to ETI by managing extracellular defense. A vast majority of the endogenous proteases discussed in this review are associated with the programmed cell death (PCD) of the infected cells and exhibit caspase-like activities. The synthesis of signal molecules, such as salicylic acid, jasmonic acid, and ethylene, and their signaling pathways, are regulated by endogenous proteases that affect the induction of pathogenesis-related genes and SAR or ISR establishment. A number of proteases are associated with herbivore defense. In this review, we summarize the data concerning identified plant endogenous proteases, their effect on plant-pathogen interactions, their subcellular localization, and their functional properties, if available, and we attribute a role in the different types and stages of innate immunity for each of the proteases covered.

Chitin-induced activation of immune signaling by the rice receptor CEBiP relies on a unique sandwich-type dimerization.

Perception of microbe-associated molecular patterns (MAMPs) through pattern recognition receptors (PRRs) triggers various defense responses in plants. This MAMP-triggered immunity plays a major role in the plant resistance against various pathogens. To clarify the molecular basis of the specific recognition of chitin oligosaccharides by the rice PRR, CEBiP (chitin-elicitor binding protein), as well as the formation and activation of the receptor complex, biochemical, NMR spectroscopic, and computational studies were performed. Deletion and domain-swapping experiments showed that the central lysine motif in the ectodomain of CEBiP is essential for the binding of chitin oligosaccharides. Epitope mapping by NMR spectroscopy indicated the preferential binding of longer-chain chitin oligosaccharides, such as heptamer-octamer, to CEBiP, and also the importance of N-acetyl groups for the binding. Molecular modeling/docking studies clarified the molecular interaction between CEBiP and chitin oligosaccharides and indicated the importance of Ile122 in the central lysine motif region for ligand binding, a notion supported by site-directed mutagenesis. Based on these results, it was indicated that two CEBiP molecules simultaneously bind to one chitin oligosaccharide from the opposite side, resulting in the dimerization of CEBiP. The model was further supported by the observations that the addition of (GlcNAc)8 induced dimerization of the ectodomain of CEBiP in vitro, and the dimerization and (GlcNAc)8-induced reactive oxygen generation were also inhibited by a unique oligosaccharide, (GlcNß1,4GlcNAc)4, which is supposed to have N-acetyl groups only on one side of the molecule. Based on these observations, we proposed a hypothetical model for the ligand-induced activation of a receptor complex, involving both CEBiP and Oryza sativa chitin-elicitor receptor kinase-1.

Take-home experience of overseas doctors at the end of their two years training placements in the International Doctors Training Programme in Obstetrics and Gynaecology in the United Kingdom: A questionnaire-based study.

This was a questionnaire-based study of overseas doctors, who came to the United Kingdom through the International Doctors Training Programme (IDTP) of Obstetrics and Gynaecology during the period of 2009-2012. The study was conducted at the end of their two-years training placement to find out what went well, what did not go well, where problems were encountered, and how they could have been avoided. We traced 48 overseas doctors, 35 (73%) responded to our questionnaire. Only 30% (9) felt that less than 50% of their expectations were met during their training period, 73.3% (22) of them received adequate help and support from their supervisors and 83.3% (25) would recommend IDTP to their colleagues. In conclusion, identification of the educational needs of international trainees, establishing a framework for their effective supervision and streamlining their training programme, in collaboration with the Royal College, regional deaneries and hosting hospitals are essential pre-requisites for overseas doctors to get the most out of their training.

The Novel NF-κB Inhibitor, MTI-II Peptide Anti-Inflammatory Drug, Suppresses Inflammatory Responses in Odontoblast-Like Cells.

Regulation of inflammation is important for pulp wound healing, including protective responses by odontoblast-like cells. However, methods for directly regulating pulp inflammation have not yet been described. The inflammatory response is mediated by a transcription factor, nuclear factor-κB (NF-κB), which activates inflammatory cytokines including tumor necrosis factor (TNF)-α. Macromolecular translocation inhibitor II (MTI-II) was previously demonstrated as an enhancer of the transcriptional activity of glucocorticoid-bound glucocorticoid receptor. Recently, a MTI-II peptide anti-inflammatory drug (MPAID) was bioengineered from the structure of MTI-II as an inhibitor of NF-κB transactivation. Here, we examined the effects of MTI-II and MPAID on the inflammatory responses of odontoblast-like cells. TNF-α inhibited alkaline phosphatase (ALP) activity, a marker of odontoblast/osteogenic differentiation, and induced NF-κB transcriptional activity in KN-3 cells, which are odontoblast-like cells derived from dental papilla cells of rat incisors, without affecting their viability. Exogenous expression of MTI-II suppressed the NF-κB transcriptional activity induced by TNF-α or overexpression of p65 (a main subunit of NF-κB) in the cells, whereas it failed to inhibit degradation of IκBα and nuclear translocation of p65 after TNF-α treatment, suggesting that MTI-II inhibits NF-κB transcriptional activity by modulating the duration of DNA binding by p65. MPAID also inhibited TNF-α-induced NF-κB transcriptional activity, the mRNA expression of IL-6 and IL-8, and IL-6 production. Furthermore, pretreatment of the cells with MPAID restored the inhibitory effect of TNF-α on ALP activity. These results suggest that MPAID may be able to regulate the inflammatory response and maintain a protective response of dental pulp. J. Cell. Biochem. 117: 2552-2558, 2016. © 2016 Wiley Periodicals, Inc.

Comparing MTI randomization procedures to blocked randomization.

Randomization is one of the cornerstones of the randomized clinical trial, and there is no shortage of methods one can use to randomize patients to treatment groups. When deciding which one to use, researchers must bear in mind that not all randomization procedures are equally adept at achieving the objective of randomization, namely, balanced treatment groups. One threat is chronological bias, and permuted blocks randomization does such a good job at controlling chronological bias that it has become the standard randomization procedure in clinical trials. But permuted blocks randomization is especially vulnerable to selection bias, so as a result, the maximum tolerated imbalance (MTI) procedures were proposed as better alternatives. In comparing the procedures, we have somewhat of a false controversy, in that actual practice goes uniformly one way (permuted blocks), whereas scientific arguments go uniformly the other way (MTI procedures). There is no argument in the literature to suggest that the permuted block design is better than or even as good as the MTI procedures, but this dearth is matched by an equivalent one regarding actual trials using the MTI procedures. So the 'controversy', if we are to call it that, pits misguided precedent against sound advice that tends to be ignored in practice. We shall review the issues to determine scientifically which of the procedures is better and, therefore, should be used.

Combining MTI-31 with RAD001 inhibits tumor growth and invasion of kidney cancer by activating autophagy.

At most of the times, patients who are diagnosed with kidney cancer should be provided with systemic treatment as drug resistance is a challenging issue in the treatment of this disease. The progression of the cancer can be inhibited with the help of mTOR inhibitors namely RAD001 (everolimus) and MTI-31. In literature, it has been revealed that these mTOR inhibitors have the potential to stimulate autophagy. This degradation pathway boosts the survival rate of the cancerous cells that are subjected to anti-cancer therapy. In this study, CCK8, colony formation assays, and ethynyl deoxyuridine (EdU) analysis were conducted to detect cell proliferation. Furthermore, Transwell assays were also conducted for cell migration analysis. In addition to these, the researchers also performed the flow cytometry process to identify the cells that are undergoing apoptosis. In vivo, experiments were conducted to measure the growth of tumors and metastasis. In this study, the treatment provided through a combination of MTI-31 and RAD001 significantly inhibited the kidney cancer cells' proliferation and tumor growth. Furthermore, there was a notable reduction in the migration and invasion of kidney cancer cells upon the neighboring cells. The outcomes from the mechanistic studies infer that the combination of MTI-31 and RAD001 increases the LC3 levels, which in turn translates into the activation of autophagy. To conclude, the combination of MTI-31 and RAD001 improves the anti-cancerous impact produced by RAD001 in vivo through the promotion of autophagy.