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Additional file 1: Supplementary Table 1. Variables assessed at enrolment and follow-up in the cohort. Supplementary Table 2. Pulmonary symptoms and test results of RA-ILD patients.

Chinese culture expects men to be strong and capable of emotional restraint, and therefore, the grief of bereaved fathers is often being overlooked in Chinese society. However, there has been little research done to understand the emotions and needs of these grief-stricken men, especially from the observations and perspectives of support professionals. This exploratory study attempted to address the knowledge gap concerning the bereaved fathers in Hong Kong through interviews of grief support workers. The study aimed at studying the needs and the pattern of grief of these fathers, plus the effects of gender and cultural expectations on their grief expression. Appropriate support and interventions were also explored. In-depth qualitative interviews were conducted with five grief support workers who had substantial experience in providing support and counseling to bereaved fathers, and reflexive thematic analysis was used in the data analysis. Results of the study showed that the bereaved fathers in Hong Kong tend to maintain their toughness and invulnerability as circumscribed by society and cultural norms amid the loss. Also, behaviors associated with the instrumental pattern of grief are more commonly observed among bereaved fathers. With respect to professional interventions, grief support workers recognized the importance of both instrumental and intuitive pattern of grief when working with the bereaved fathers and indicated that they had greater success in engaging these fathers through culturally-sensitive practice by paying attention to the societal and cultural expectations on men and respecting the fathers’ preferred choice and priority in the grief process. KEYWORDS: fathers’ grief, Chinese men, pattern of grief, Hong Kong, grief counseling, grief support workers, bereavement

Recovery is a progressive process involving support to people with mental illness to take control of their life through the enhancement of motivation, self-drive, and responsibility. Drawing on qualitative interviews with 61 patients with mental illness aged between 40 and 75 in the community or residential settings, this study examined the wishes and hopes of clients who were in recovery. Participants described wishes and hopes for autonomy and independence in finances, accommodation, and health; stable housing or accommodation; meaningful occupation or employment; ‘giving back’ to society by serving others; intimate relationships; and gaining back ‘lost time.’ Wishes and hopes were motivating factors contributing to physical, mental, and social health over time, motivating clients with mental illness to live happily. To foster recovery, mental health practitioners should consider the identification and fulfilment of wishes and hopes in health and social care programs for this unique client group.

Objectives: Research evidence has demonstrated disparities and barriers associated with mental illness, which creates challenges for individuals with mental illness to maintain physical, mental, and social health as they age. The aim of this study was to examine the meaning of aging from the perspective of individuals with mental illness and explore their motivations and challenges to adopting healthy aging lifestyles and practices.Method: Using a qualitative narrative inquiry approach, interviews were conducted with 61 aging patients with mental illness aged 40 and older in community and institutional settings in Hong Kong.Results: Participants discussed the meaning of healthy aging in terms of meaningful occupation and use of time, and independence and autonomy. Motivating factors included a desire to avoid 'burdening' other people, to 'give back' to society, and gain back 'lost time'. These were connected to strategies for healthy aging, including social relationships and activities, spirituality, and healthy lifestyles. Challenges to adopting healthy aging practices included physical health difficulties and medication side effects, lack of purpose and boredom associated with daily routines and use of time, and conflicts and loss affecting family and peer relationships.Conclusion: Social and health services should be tailored to support aging individuals with mental illness and their families, addressing motivations and barriers to adopting healthy lifestyles. Promoting healthy aging practices to enable individuals with mental illness to achieve healthy aging is important for preparing for the aging of this population.

Additional file 1:. Supplemental Figure 1 and Table 1

Additional file 2:. Supplementary methods and results

Significance Homologous recombination (HR) repairs DNA double-strand breaks by using a homologous template to retrieve sequence information lost at the break site. The broken DNA molecule first engages with the homologous donor molecule and is then separated from it to complete the process. Depending on the HR subpathways used, the separation step can lead to crossovers (COs) between the participating molecules. Such events can cause genomic alterations and eventually cancer if a donor molecule other than the identical sister chromatid is used. Here, we characterize two subpathways of HR with different propensities to form COs. We show the unexpected dominance of the CO-forming subpathway and characterize the processes involved in CO formation and subpathway choice in cancer and normal, untransformed cells., Homologous recombination (HR) is an important DNA double-strand break (DSB) repair pathway that copies sequence information lost at the break site from an undamaged homologous template. This involves the formation of a recombination structure that is processed to restore the original sequence but also harbors the potential for crossover (CO) formation between the participating molecules. Synthesis-dependent strand annealing (SDSA) is an HR subpathway that prevents CO formation and is thought to predominate in mammalian cells. The chromatin remodeler ATRX promotes an alternative HR subpathway that has the potential to form COs. Here, we show that ATRX-dependent HR outcompetes RECQ5-dependent SDSA for the repair of most two-ended DSBs in human cells and leads to the frequent formation of COs, assessed by measuring sister chromatid exchanges (SCEs). We provide evidence that subpathway choice is dependent on interaction of both ATRX and RECQ5 with proliferating cell nuclear antigen. We also show that the subpathway usage varies among different cancer cell lines and compare it to untransformed cells. We further observe HR intermediates arising as ionizing radiation (IR)-induced ultra-fine bridges only in cells expressing ATRX and lacking MUS81 and GEN1. Consistently, damage-induced MUS81 recruitment is only observed in ATRX-expressing cells. Cells lacking BLM show similar MUS81 recruitment and IR-induced SCE formation as control cells. Collectively, these results suggest that the ATRX pathway involves the formation of HR intermediates whose processing is entirely dependent on MUS81 and GEN1 and independent of BLM. We propose that the predominant ATRX-dependent HR subpathway forms joint molecules distinct from classical Holliday junctions.

This chapter uses the case study of Hong Kong to explore innovative ways to enhance students’ and other stakeholders’ knowledge and skills in working with ethnic minority service users. The chapter begins with important background information about the needs of ethnic minority populations in Hong Kong. The second half of the chapter then focuses on issues of social work education, drawing upon international and national literature to set the scene for an explanation about the planning and delivery of e-learning videos to enable social work students to challenge aspects of discrimination and racism in Hong Kong. The chapter concludes with an appeal for more innovative approaches to social work education, policy and practice in order that the needs of ethnic minority service users are met in Hong Kong.

A new modality – the small group learning approach, was developed for social group work courses for social work students in Hong Kong. A research study, aimed at understanding the students’ level ...

Summary Homologous recombination (HR) is essential for high-fidelity DNA repair during mitotic proliferation and meiosis. Yet, context-specific modifications must tailor the recombination machinery to avoid (mitosis) or enforce (meiosis) the formation of reciprocal exchanges—crossovers—between recombining chromosomes. To obtain molecular insight into how crossover control is achieved, we affinity purified 7 DNA-processing enzymes that channel HR intermediates into crossovers or noncrossovers from vegetative cells or cells undergoing meiosis. Using mass spectrometry, we provide a global characterization of their composition and reveal mitosis- and meiosis-specific modules in the interaction networks. Functional analyses of meiosis-specific interactors of MutLγ-Exo1 identified Rtk1, Caf120, and Chd1 as regulators of crossing-over. Chd1, which transiently associates with Exo1 at the prophase-to-metaphase I transition, enables the formation of MutLγ-dependent crossovers through its conserved ability to bind and displace nucleosomes. Thus, rewiring of the HR network, coupled to chromatin remodeling, promotes context-specific control of the recombination outcome., Graphical Abstract, Highlights • Affinity proteomics reveals the composition and interaction landscape of HR enzymes • Interaction network rewiring of HR enzymes during mitotic proliferation and meiosis • Chd1, Rtk1, and Caf120 regulate meiotic crossing-over • Chd1 remodels chromatin to enable formation of MutLγ-Exo1-dependent crossovers, Wild et al. used affinity proteomics to characterize the composition and interaction landscape of 7 DNA repair enzymes during mitotic proliferation and meiosis. They report a concerted and context-specific rewiring of the interactomes and reveal meiosis-specific network components with roles in crossing-over.

Introduction The Mini-Cog is an easy-to-administer and reliable short screen for possible dementia. It is said to have high sensitivity and specificity comparable to those of Mini Mental Status Examination (MMSE). It consists of a delayed-recall (DR) test and a distractor-clock-drawing test (CDT). A positive screen is defined as either a score of zero in the 3-item DR or a score of 1–2 in the DR combined with an abnormal CDT. The Mini-Cog is said to be relatively free of language, educational and cultural bias. However the utility of the Mini-Cog for screening ethnic elders with minimal or no education remains largely unexplored. Methods Ninety-six community-dwelling Chinese elders from 7 social-recreational programs in Toronto were recruited and screened by the Mini-Cog for possible dementia. The feasibility and limitations of using the Mini-Cog for screening were evaluated. Participants' feedback on the acceptability of the Mini-Cog and their resistance to future Mini-Cog screening were collected through evaluative questionnaires. Fisher Exact test was used to determine whether there was significant association between participants' refusal to attempt or complete the Mini-Cog and each of the pertinent variables namely 1) participants' literacy; 2) resistance to the Mini-Cog re-screening; 3) difficulty understanding the Mini-Cog instruction; and 4) performance on the DR part of the Mini-Cog. Results Of the 96 participants, 10 (10.4%) refused to attempt the CDT part of the Mini-Cog, and expressed difficulty in writing and drawing. Of those 10, 7 reported having no education and 3 minimal education. A highly significant association was found between participants' refusal to attempt CDT and illiteracy ( p =7E−0; p p =0.4958; p Conclusion The results suggest that there may be limitations in the utility of the Mini-Cog for screening elders with minimal education. This concurs with earlier findings about the negative effect of illiteracy on CDT performance. Further study is needed to explore possible modifications to the distracter component of the Mini-Cog for elders who are illiterate or have a very low level of education.

We study one-dimensional wave equations defined by a class of fractal Laplacians. These Laplacians are defined by fractal measures generated by iterated function systems with overlaps, such as the well-known infinite Bernoulli convolution associated with the golden ratio and the 3-fold convolution of the Cantor measure. The iterated function systems defining these measures do not satisfy the post-critically finite condition or the open set condition. By using second-order self-similar identities introduced by Strichartz et al., we discretize the equations and use the finite element and central difference methods to obtain numerical approximations to the weak solutions. We prove that the numerical solutions converge to the weak solution, and obtain estimates for the rate of convergence.

MicroRNA is known to be an important regulator of gene expression. The microRNAs that were found to be differentially expressed in normal urothelium and urothelial carcinomas in the literature were selected and meaningful microRNAs were validated using urothelial tumor cells lines; formalin-fixed and paraffin-embedded (FFPE) tissues; and urine samples for both the definitely benign and malignant categories. Diagnostic utility was also assessed by applying validated microRNAs to urine specimens in the "atypical urothelial cells" category of the Paris System for Reporting Urine Cytology. Among the 25 consistently directed microRNAs in 2 or more studies, 14 microRNAs were upregulated and 11 downregulated. In urothelial tumor cell lines, 3 microRNAs were upregulated and 8 microRNAs were downregulated. In the step using FFPE tissues, four microRNAs (miR-145, miR-133a, miR-125b, and miR-99a) levels were downregulated and four microRNAs (miR-96, miR-141, miR-200c, and miR-205) were upregulated in the entire spectrum of urothelial neoplasms. Similar expression profiles were observed in urine specimens of "negative for high-grade urothelial carcinoma" and "urothelial carcinoma". The expression of miR-99a revealed different trends among the atypical urothelial categories. The findings from this study show that consistently upregulated or downregulated microRNAs might be involved in tumorigenesis or progression of urothelial carcinoma and that they could be used as potential diagnostic or prognostic markers.

We consider time domain electromagnetic scattering from a bounded homogeneous penetrable obstacle. The problem is reduced to a system of time dependent integral equations on the boundary of the scatterer. Using convolution quadrature in time and a Galerkin method on the boundary we derive error estimates for the fully discrete system of boundary integral equations. This is accomplished by proving parameter dependent estimates for the discrete and continuous integral equation system in the Laplace transform domain. In particular a non-standard transmission problem is analyzed. Besides the error estimates, the paper provides a useful extension result and estimates for the spatially semi-discrete problem.

Objective Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant immune system aberrations resulting from complex heritable genetics as well as environmental factors. We undertook to study the role of TRAF6 as a candidate gene for SLE, since it plays a major role in several signaling pathways that are important for immunity and organ development. Methods Fifteen single-nucleotide polymorphisms (SNPs) across TRAF6 were evaluated in 7,490 SLE patients and 6,780 control subjects from different ancestries. Population-based case-control association analyses and meta-analyses were performed. P values, false discovery rate q values, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated. Results Evidence of associations was detected in multiple SNPs. The best overall P values were obtained for SNPs rs5030437 and rs4755453 (P = 7.85 × 10 -5 and P = 4.73 × 10 -5, respectively) without significant heterogeneity among populations (P = 0.67 and P = 0.50, respectively, in Q statistic). In addition, SNP rs540386, which was previously reported to be associated with rheumatoid arthritis (RA), was found to be in linkage disequilibrium with these 2 SNPs (r 2 = 0.95) and demonstrated evidence of association with SLE in the same direction (meta-analysis P = 9.15 × 10 -4, OR 0.89 [95% CI 0.83-0.95]). The presence of thrombocytopenia improved the overall results in different populations (meta-analysis P = 1.99 × 10 -6, OR 0.57 [95% CI 0.45-0.72], for rs5030470). Finally, evidence of family-based association in 34 African American pedigrees with the presence of thrombocytopenia was detected in 1 available SNP (rs5030437) with a Z score magnitude of 2.28 (P = 0.02) under a dominant model. Conclusion Our data indicate the presence of association of TRAF6 with SLE, consistent with the previous report of association with RA. These data provide further support for the involvement of TRAF6 in the pathogenesis of autoimmunity. Copyright © 2012 by the American College of Rheumatology.

Several replication-initiation proteins are assembled stepwise onto replicators to form pre-replicative complexes (pre-RCs) to license eukaryotic DNA replication. We performed a yeast functional proteomic screen and identified the Rix1 complex members (Ipi1p-Ipi2p/Rix1-Ipi3p) as pre-RC components and critical determinants of replication licensing and replication-initiation frequency. Ipi3p interacts with pre-RC proteins, binds chromatin predominantly at ARS sequences in a cell cycle-regulated and ORC- and Noc3p-dependent manner and is required for loading Cdc6p, Cdt1p and MCM onto chromatin to form pre-RC during the M-to-G₁ transition and for pre-RC maintenance in G₁ phase-independent of its role in ribosome biogenesis. Moreover, Ipi1p and Ipi2p, but not other ribosome biogenesis proteins Rea1p and Utp1p, are also required for pre-RC formation and maintenance, and Ipi1p, -2p and -3p are interdependent for their chromatin association and function in pre-RC formation. These results establish a new framework for the hierarchy of pre-RC proteins, where the Ipi1p-2p-3p complex provides a critical link between ORC-Noc3p and Cdc6p-Cdt1p-MCM in replication licensing.

DNA replication in eukaryotic cells is tightly regulated to ensure faithful inheritance of the genetic material. While the replicators, replication origins and many replication-initiation proteins in Saccharomyces cerevisiae have been identified and extensively studied, the detailed mechanism that controls the initiation of DNA replication is still not well understood. It is likely that some factors involved in or regulating the initiation of DNA replication have not been discovered. To identify novel DNA replication-initiation proteins and their regulators, we developed a sensitive and comprehensive phenotypic screen by combining several established genetic strategies including plasmid loss assays with plasmids containing a single versus multiple replication origins and colony color sectoring assays. We isolated dozen of mutants in previously known initiation proteins and identified several novel factors, including Ctf1p Ctf3p, Ctf4p, Ctf18p, Adk1p and Cdc60p, whose mutants lose plasmid containing a single replication origin at high rates but lose plasmid carrying multiple replication origins at lower rates. We also show that overexpression of replication initiation proteins causes synthetic dosage lethality or growth defects in ctf1 and ctf18 mutants and that Ctf1p and Ctf18p physically interact with ORC, Cdt1p and MCM proteins. Furthermore, depletion of both Ctf1p and Ctf18p prevents S phase entry, retards S phase progression, and reduces pre-RC formation during the M-to-G₁ transition. These data suggest that Ctf1p and Ctf18p together play important roles in regulating the initiation of DNA replication.

Homozygous deletion screening has been widely utilized to define tumour suppressor genes (TSGs) in cancers. Although these biallelic deletions are infrequent, their identification has facilitated the discovery of many important TSGs. We have systematically examined the genome of hepatocellular carcinoma (HCC), a highly malignant tumour that is rapidly fatal, for the presence of homozygous deletions. Array-CGH analysis on early passage of HCC cultures and cell lines led us to identify six homozygous deleted (HD) regions. A high concordance between array-CGH and expression of HD genes was demonstrated, where crystallin Lambda1 (CRYL1; located on chromosome 13q12.11) displayed the most frequent down-regulation. We found that reduced mRNA expression of CRYL1 was common in HCC tumours when compared with their adjacent non-tumoural liver (p = 0.0097). Significant associations could also be drawn between repressed CRYL1 and advanced tumour staging, increased tumour size, and shorter disease-free survival of patients (p < 0.037). Moreover, homozygous deletions on CRYL1 could be detected in 36% of HCC cases, where recurrent HDs were identified on exons 1, 5, and 8. Examination of other causal events suggested histone deacetylation and promoter hypermethylation to be likely inactivating mechanisms as well. Re-expression of CRYL1 in the SK-Hep1 cell line, where biallelic loss of CRYL1 was found, induced profound inhibition of cellular proliferation and cell growth (p < 0.0015). By Annexin V staining, CRYL1 restoration readily increased pro-apoptotic cells with an induction of PARP cleavage. Flow cytometry further revealed that CRYL1 could prolong the G(2)-M phase, possibly through interruption of the Cdc2/cyclin B pathway. Given that regional chromosome 13q12-q14 loss is a causal genomic event in HCC tumourigenesis, our finding may have implications for identifying a novel TSG CRYL1 within this important locus.

The difficulty associate with maintaining live squids for two days or more severely limits the geographic area and time over which they can be distribute and sold. The cases of death during transportation are not yet clearly understood, but it is thought to be due to the physical damage they inflict on each other, the stress of competition for space, stress due rapid changes of surroundings or by combination of these factors. We investigated the damage to gills due to a shortage in the dissolved oxygen (DO) in water to examine its possible contributions to the cause of the death. Deformations in the protruding quasi-lamellae of the gill were measured for different DO levels by megascopic and microscopic observations. The experiments were conducted on the USHIO MARU training-ship outside HAKODATE port, using squids caught by angling. Squids were maintained in boxes (20 cm×42 cm×22 cm) with 8 L of water, and aeration was stopped at the beginning of the test. The DO in the water decreased slowly in response to respiration of the squid, which died approximately after three hours by a shortage of oxygen. Behavioral observations showed that squids were initially active in the box. Once oxygen decreased to approximately 6 mg/L, squids remained motionless near the bottom of the box that might be due in response to a shortage of oxygen. Squids kept this behavior for two or three hours depending on the temperature. Although squids did not move in this period, they reacted to external stimulations, such as touch, or changes in light. Then, their body color changed to white and they died. Gill damage was compared in three categories: (1) initial DO, (2) half DO and (3) Low DO. Gills were surgically removed and preserved in formalin until such observations in the laboratory. The number of deformation of quasi-lamellae was counted, and the extent of the protrusion was measured using microscope and by viewing. The extent of deformations differed significantly depend on the shortage of DO.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive dysfunction and degeneration of motor neurons in the central nervous system (CNS). In the absence of effective drug treatments for ALS, stem cell treatment has emerged as a candidate therapy for this disease. To date, however, there is no consensus protocol that stipulates stem cell types, transplantation timing, or frequency. Using an ALS mouse model carrying a high copy number of a mutant human superoxide dismutase-1 (SOD1)G93A transgene, we investigated the effect of neural induction on the innate therapeutic potential of mesenchymal stem cells (MSCs) in relation to preclinical transplantation parameters. In our study, the expression of monocyte chemoattractant protein-1 (MCP-1) was elevated in the ALS mouse spinal cord. Neural induction of MSCs with neurogenin 1 (Ngn1) upregulated the expression level of the MCP-1 receptor, CCR2, and enhanced the migration activity toward MCP-1 in vitro. Ngn1-expressing MSCs (MSCs-Ngn1) showed a corresponding increase in tropism to the CNS after systemic transplantation in ALS mice. Notably, MSCs-Ngn1 delayed disease onset if transplanted during preonset ages, whereas unprocessed MSCs failed to do so. If transplanted near the onset ages, a single treatment with MSCs-Ngn1 was sufficient to enhance motor functions during the symptomatic period (15–17 weeks), whereas unprocessed MSCs required repeated transplantation to achieve similar levels of motor function improvement. Our data indicate that systemically transplanted MSCs-Ngn1 can migrate to the CNS and exert beneficial effects on host neural cells for an extended period of time through paracrine functions, suggesting a potential benefit of neural induction of transplanted MSCs in long-term treatment of ALS.

Network analysis-based module detection has significant implications in many fields. In cellular/ molecular biology, module detection based on analyses of metabolic/regulatory networks will not only help us understand more about the function and evolution of cellular machinery of an organism, but will also provide tractable contextual information for potential drug targets and facilitate improvements in drug designs. We here present our preliminary study on the module detection for bacteria based on the spectral clustering of the protein-protein functional association networks. We first examined how the parameter of the spectral clustering algorithm (i.e., the number of clusters) affects our module detection results, and demonstrated that when the number of clusters was set too small or too large the resulting module collection deteriorate in terms of gene coverage and intra-module association. We then compared our predicted modules against the randomly generated modules, and demonstrated that our modules (i) have a higher ratio of the intra-module to inter-module gene-gene functional association scores and (ii) can better capture the modularization information inherent in the experimentally verified modules. Finally we compared the module collections of seven bacterial organisms, and observed that modules related to membrane transport and cell motility are among those that are conserved among multiple organisms. Because it is desirable from both scientific and technical points of view to study functional modules at various resolution levels, we believe that the spectral clustering algorithm, with the flexibility rendered by different parameter settings, provides an appropriate solution in terms of capturing the modularization properties of networks and computational affordability.

Homozygous deletion screening has been widely utilized to define tumour suppressor genes (TSGs) in cancers. Although these biallelic deletions are infrequent, their identification has facilitated the discovery of many important TSGs. We have systematically examined the genome of hepatocellular carcinoma (HCC), a highly malignant tumour that is rapidly fatal, for the presence of homozygous deletions. Array-CGH analysis on early passage of HCC cultures and cell lines led us to identify six homozygous deleted (HD) regions. A high concordance between array-CGH and expression of HD genes was demonstrated, where crystallin Lambda1 (CRYL1; located on chromosome 13q12.11) displayed the most frequent down-regulation. We found that reduced mRNA expression of CRYL1 was common in HCC tumours when compared with their adjacent non-tumoural liver (p = 0.0097). Significant associations could also be drawn between repressed CRYL1 and advanced tumour staging, increased tumour size, and shorter disease-free survival of patients (p0.037). Moreover, homozygous deletions on CRYL1 could be detected in 36% of HCC cases, where recurrent HDs were identified on exons 1, 5, and 8. Examination of other causal events suggested histone deacetylation and promoter hypermethylation to be likely inactivating mechanisms as well. Re-expression of CRYL1 in the SK-Hep1 cell line, where biallelic loss of CRYL1 was found, induced profound inhibition of cellular proliferation and cell growth (p0.0015). By Annexin V staining, CRYL1 restoration readily increased pro-apoptotic cells with an induction of PARP cleavage. Flow cytometry further revealed that CRYL1 could prolong the G(2)-M phase, possibly through interruption of the Cdc2/cyclin B pathway. Given that regional chromosome 13q12-q14 loss is a causal genomic event in HCC tumourigenesis, our finding may have implications for identifying a novel TSG CRYL1 within this important locus.

The objective of this study was to develop a Korean version of the Assessment of Spondyloarthritis International Society-Health Index/Environmental Factor (ASAS HI/EF) and to evaluate its reliability and validity in Korean patients with axial spondyloarthritis (SpA). A total of 43 patients participated. Translation and cross-cultural adaptation of the ASAS HI/EF was performed according to international standardized guidelines. We also evaluated validity by calculating correlation coefficients between the ASAS-HI/EF score and the clinical parameters. Test-retest reliability was excellent. The correlations among the mean ASAS-HI score and all tools of assessment for SpA were significant. When it came to construct validity, the ASAS HI score was correlated with nocturnal back pain, spinal pain, patients's global assessment score, the Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis metrology index (BASMI) and EuroQoL visual analogue scale (EQ VAS) (r = 0.353, 0.585, 0.598, 0.637, 0.690, 0.430, and -0.534). The ASAS EF score was also correlated with the patient's global assessment's score, BASDAI, BASFI, BASMI, and EQ VAS score (r = 0.375, 0.490, 0.684, 0.485, and -0.554). The Korean version of the ASAS HI/EF can be used in the clinical field to assess and evaluate the state of health of Korean axial SpA patients. Graphical Abstract

Purpose: The p53 tumor suppressor gene is believed to play a pivotal role in preventing the uncontrolled cellular growth characteristic of cancer. Mutation of the p53 gene represent one of the most common genetic alterations in human cancers, and the acquisition of such defects is strongly associated with tumor progression and metastasis. The aim of this study was to evaluate the relation between p53 immunoreactivity and the mutation of p53 gene in gastric adenocarcinoma obtained by laser capture microscope. Materials and Methods: Formalin fixed paraffin embedded tissue specimens were obtained from 20 patients who underwent surgery for gastric cancer. According to UICC TNM system, 3 of the cases were Ia, 2 cases II, 4 cases IIIa, 5 cases IIIb, and 6 cases IV. Results: Immunohistochemical staining revealed eight cases as negative (less than ), twelve cases as postive (more than ). The locations of mutations were as follows; 7 cases had point mutation at exon 4, and 3 cases point mutation at exon 8. There was no mutation at exon 5, 6, 7 and 9. The mutation was observed in 1 case out of 8 p53 oncoprotein negative cases, and 7 cases out of 12 p53 positive cases. The mutation was more common in p53 positive cases (P

Cellular behaviors, such as differentiation, are regulated by complex ligation processes involving cell surface receptors, which can be activated by various divalent metal cations. The design of nanoparticle for co-delivery of ligand and ligation activator can offer a novel strategy to synergistically stimulate ligation processes in vivo. Here, we present a novel layered double hydroxide (LDH)-based nanohybrid (MgFe-Ado-LDH), composed of layered MgFe hydroxide nanocarriers sandwiching the adenosine cargo molecule, maintained through an electrostatic balance, to co-deliver the adenosine (Ado) ligand from the interlayer spacing and the Mg 2+ ion (ligation activator) through the dissolution of the MgFe nanocarrier itself. Our findings demonstrate that the MgFe-Ado-LDH nanohybrid promoted osteogenic differentiation of stem cells through the synergistic activation of adenosine A2b receptor (A2bR) by the dual delivery of adenosine and Mg 2+ ions, outperforming direct supplementation of adenosine alone. Furthermore, the injection of the MgFe-Ado-LDH nanohybrid and stem cells embedded within hydrogels promoted the healing of rat tibial bone defects through the rapid formation of fully integrated neo-bone tissue through the activation of A2bR. The newly formed bone tissue displayed the key features of native bone, including calcification, mature tissue morphology, and vascularization. This study demonstrates a novel and effective strategy of bifunctional nanocarrier-mediated delivery of ligand (cargo molecule) and activation of its ligation to receptor by the nanocarrier itself for synergistically inducing stem cell differentiation and tissue healing in vivo, thus offering novel design of biomaterials for regenerative medicine. Refereed/Peer-reviewed