Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development

<p>Abstract</p> <p>Background</p> <p>Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development.</p> <p>Objective</p> <p>The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development.</p> <p>Methods</p> <p>ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON⁺(with at least one ON lesion) group and ON^-(without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON⁺rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion).</p> <p>Results</p> <p>Local intra-osseous perfusion index was found lower in either ON⁺or MON group when compared to either ON^-or SON group, whereas the marrow fat cells number and area were much larger in either ON⁺or MON group as compared with ON^-and SON group. The adipogenic differentiation ability of MSCs and PPARγ2 expression in either ON⁺or MON group were elevated significantly as compared with either ON^-or SON group.</p> <p>Conclusion</p> <p>These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.</p

A pilot controlled trial of a combination of dense cranial electroacupuncture stimulation and body acupuncture for post-stroke depression

BACKGROUND: Our previous studies have demonstrated the treatment benefits of dense cranial electroacupuncture stimulation (DCEAS), a novel brain stimulation therapy in patients with major depression, postpartum depression and obsessive-compulsive disorder. The purpose of the present study was to further evaluate the effectiveness of DCEAS combined with body acupuncture and selective serotonin reuptake inhibitors (SSRIs) in patients with post-stroke depression (PSD). METHODS: In a single-blind, randomized controlled trial, 43 patients with PSD were randomly assigned to 12 sessions of DCEAS plus SSRI plus body electroacupuncture (n = 23), or sham (non-invasive cranial electroacupuncture, n-CEA) plus SSRI plus body electroacupuncture (n = 20) for 3 sessions per week over 4 weeks. Treatment outcomes were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), the Clinical Global Impression - Severity scale (CGI-S) and Barthel Index (BI), a measure used to evaluate movement ability associated with daily self-caring activity. RESULTS: DCEAS produced a significantly greater reduction of both HAMD-17 and CGI-S as early as week 1 and CGI-S at endpoint compared to n-CEA, but subjects of n-CEA group exhibited a significantly greater improvement on BI at week 4 than DCEAS. Incidence of adverse events was not different in the two groups. CONCLUSIONS: These results indicate that DCEAS could be effective in reducing stroke patients’ depressive symptoms. Superficial electrical stimulation in n-CEA group may be beneficial in improving movement disability of stroke patients. A combination of DCEAS and body acupuncture can be considered a treatment option for neuropsychiatric sequelae of stroke. TRIAL REGISTRATION: http://www.clinicaltrials.gov, NCT01174394

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

The impact of trisomy 21 on epidemiology, management, and outcomes of congenital duodenal obstruction: a population-based study

Abstract: Purpose: Congenital duodenal obstruction (CDO) is associated with trisomy 21 (T21), or Down’s syndrome, in around a third of infants. The aim of this study was to explore the impact of T21 on the epidemiology, management, and outcomes of infants with CDO. Methods: Data were prospectively collected from specialist neonatal surgical centres in the United Kingdom over a 12 month period from March 2016 using established population-based methodology for all babies with CDO. Infants with T21 were compared to those without any chromosomal anomaly. Results: Of 102 infants with CDO that underwent operative repair, T21 was present in 33 [32% (95% CI 23–41%)] babies. Cardiac anomalies were more common in those with T21 compared to those without a chromosomal anomaly (91 vs 17%, p < 0.001), whereas associated gastrointestinal anomalies were less common in infants with T21 (3 vs 12%, p = 0.03). Surgical management was not influenced by T21. Time to achieve full enteral feed, need for repeat related surgery, and mortality were similar between groups. Infants with T21 had a longer median initial inpatient stay (23 vs 16.5 days, p = 0.02). Conclusions: Infants with T21 have a higher incidence of cardiac anomalies and a longer initial inpatient stay; however, it does not change CDO management or outcomes. This information is important for prenatal and postnatal counselling of parents of infants with CDO and T21

The impact of trisomy 21 on epidemiology, management, and outcomes of congenital duodenal obstruction: a population-based study

Abstract: Purpose: Congenital duodenal obstruction (CDO) is associated with trisomy 21 (T21), or Down’s syndrome, in around a third of infants. The aim of this study was to explore the impact of T21 on the epidemiology, management, and outcomes of infants with CDO. Methods: Data were prospectively collected from specialist neonatal surgical centres in the United Kingdom over a 12 month period from March 2016 using established population-based methodology for all babies with CDO. Infants with T21 were compared to those without any chromosomal anomaly. Results: Of 102 infants with CDO that underwent operative repair, T21 was present in 33 [32% (95% CI 23–41%)] babies. Cardiac anomalies were more common in those with T21 compared to those without a chromosomal anomaly (91 vs 17%, p < 0.001), whereas associated gastrointestinal anomalies were less common in infants with T21 (3 vs 12%, p = 0.03). Surgical management was not influenced by T21. Time to achieve full enteral feed, need for repeat related surgery, and mortality were similar between groups. Infants with T21 had a longer median initial inpatient stay (23 vs 16.5 days, p = 0.02). Conclusions: Infants with T21 have a higher incidence of cardiac anomalies and a longer initial inpatient stay; however, it does not change CDO management or outcomes. This information is important for prenatal and postnatal counselling of parents of infants with CDO and T21

Functional crosstalk between chromatin and hypoxia signalling

Eukaryotic genomes are organised in a structure called chromatin, comprising of DNA and histone proteins. Chromatin is thus a fundamental regulator of gene expression, as it offers storage and protection but also controls accessibility to DNA. Sensing and responding to reductions in oxygen availability (hypoxia) have recognised importance in both physiological and pathological processes in multicellular organisms. One of the main mechanisms controlling these responses is control of gene expression. Recent findings in the field of hypoxia have highlighted how oxygen and chromatin are intricately linked. This review will focus on mechanisms controlling chromatin in hypoxia, including chromatin regulators such as histone modifications and chromatin remodellers. It will also highlight how these are integrated with hypoxia inducible factors and the knowledge gaps that persist

Housing design and testing of a surgical robot developed for orthopaedic surgery

Background/Objective: Surgical technology has advanced rapidly with the introduction of robot technology. Apart from mechanical and electronic elements, housing design is an essential component that must be thoughtfully considered, bearing in mind the general requirements for medical devices used in operating theatres. The aim of this study was to design a modern and safe housing for a surgical robotic system for orthopaedic applications in Hong Kong that would meet the general requirements for obtaining local regulatory body approval. Methods: Based on the general requirements for Class II Medical Devices, industrial product designers worked in close collaboration with a robot research team formed by engineers and orthopaedic surgeons to design a modern and safe housing for the HybriDot® Surgical Robotic System that performs computer-assisted surgery. Results: The design received local regulatory body approval for its application in operating theatres and was approved for orthopaedic surgery in Hong Kong after fulfilling the general requirements for safety, accuracy, movability and operability. Conclusion: This project demonstrated a good model of multidisciplinary R&D of surgical robotics led by orthopaedic surgeons, in collaboration with mechanical and electronic engineers and industrial designers