One-year outcomes of an osteoporosis liaison services program initiated within a healthcare system.

Due to the huge gap in the care of patients with osteoporosis and fragility fractures, we aimed to explore the effectiveness of the osteoporosis liaison service (OLS) in osteoporosis care. We found that OLS can improve osteoporosis care, including increasing medication compliance, increasing calcium/vitamin D/protein intake, and reducing fall rate. INTRODUCTION: A significant gap exists in the care of patients with osteoporosis and fragility fractures. This study aimed to evaluate 1-year outcomes of an osteoporosis liaison service (OLS) program that includes two independent components: medication management services (MMS) to improve medication adherence and fracture liaison services (FLS) for secondary prevention. METHODS: Patients with new hip fracture or untreated vertebral fractures enrolled in the FLS program (n = 600), and those with osteoporosis medication management issues but not necessarily fragility fractures enrolled in the MMS program (n = 499) were included. To evaluate outcomes, care coordinators assessed baseline items adapted from the 13 Best Practices Framework (BPF) standards of the International Osteoporosis Foundation, with telephone follow-up every 4 months for 1 year. RESULTS: Mean age of this cohort was 76.2 ± 10.3 years, 78.8% were female. After 1-year participation in the program, all patients had received bone mineral density tests, and medication adherence for the entire cohort at 12 months was 91.9 ± 19.6%, with significant improvement in fall rates (23.4% reduction), exercise rates (16.8% increase), calcium intake (26.5% increase), vitamin D intake (26.4% increase), and adequate protein intake (17.3% increase) (all p < 0.05). After 1-year OLS program, the overall rates of mortality, incident fracture, and falls were 6.6%, 4.0%, and 24.3%, respectively. CONCLUSIONS: The OLS program is associated with improved osteoporosis care, including increased medication adherence, calcium/vitamin D and protein intake, and reduced fall rate.

Clinical implications of head-shaking nystagmus in central and peripheral vestibular disorders: is perverted head-shaking nystagmus specific for central vestibular pathology?

BACKGROUND AND PURPOSE: The patterns of head-shaking nystagmus (HSN) aid in differentiation between central and peripheral vestibular disorders, and perverted HSN (pHSN) has been considered a central sign. The aim was to determine the characteristics of HSN in a large number of patients with either peripheral or central vestibular disorders in a dizziness clinic of a university hospital. METHODS: The medical records of 7544 dizzy patients were reviewed during a year and 822 patients with a clinical diagnosis of vestibular disorders were recruited. The findings of spontaneous nystagmus (SN) and HSN in these patients were compared with those of healthy controls (n = 48). RESULTS: A total of 217 of the 822 patients (26.4%) were classified as having a central vestibular disorder, whilst 397 (48.3%) had a peripheral vestibular disorder. In the peripheral vestibular disorder group, SN was observed in 14.1% and HSN in 40.8%, amongst whom 24.1% were the pHSN form. In the central group, SN was observed in 17.5% and HSN in 24.0% of whom 57.7% was pHSN. HSN was more frequently observed in the peripheral vestibular disorder group than in the central group (40.8% vs. 24.0%, P < 0.01). However, the proportion of pHSN was significantly increased in the central group compared to the peripheral vestibular patient group (57.7% vs. 24.1%, P < 0.01). CONCLUSIONS: Since pHSN is not specific for central vestibular disorders, other clinical features should be considered in pursuing a central lesion in patients with pHSN.

[An interlaboratory comparison study on the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels].

Objective: To investigate the current status and real performance of the detection of RUNX1-RUNX1T1 fusion transcript levels and WT1 transcript levels in China through interlaboratory comparison. Methods: Peking University People's Hospital (PKUPH) prepared the samples for comparison. That is, the fresh RUNX1-RUNX1T1 positive (+) bone morrow nucleated cells were serially diluted with RUNX1-RUNX1T1 negative (-) nucleated cells from different patients. Totally 23 sets with 14 different samples per set were prepared. TRIzol reagent was added in each tube and thoroughly mixed with cells for homogenization. Each laboratory simultaneously tested RUNX1-RUNX1T1 and WT1 transcript levels of one set of samples by real-time quantitative PCR method. All transcript levels were reported as the percentage of RUNX1-RUNX1T1 or WT1 transcript copies/ABL copies. Spearman correlation coefficient between the reported transcript levels of each participated laboratory and those of PKUPH was calculated. Results: ①RUNX1-RUNX1T1 comparison: 9 samples were (+) and 5 were (-) , the false negative and positive rates of the 20 participated laboratories were 0 (0/180) and 5% (5/100) , respectively. The reported transcript levels of all 9 positive samples were different among laboratories. The median reported transcript levels of 9 positive samples were from 0.060% to 176.7%, which covered 3.5-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.5 to 12.3 (one result which obviously deviated from other laboratories' results was not included) , 85% (17/20) of the laboratories had correlation coefficient ≥0.98. ②WT1 comparison: The median reported transcript levels of all 14 samples were from 0.17% to 67.6%, which covered 2.6-log. The ratios of each sample's highest to the lowest reported transcript levels were from 5.3-13.7, 62% (13/21) of the laboratories had correlation coefficient ≥0.98. ③ The relative relationship of the reported RUNX1-RUNX1T1 transcript levels between the participants and PKUPH was not always consistent with that of WT1 transcript levels. Both RUNX1-RUNX1T1 and WT1 transcript levels from 2 and 7 laboratories were individually lower than and higher than those of PKUPH, whereas for the rest 11 laboratories, one transcript level was higher than and the other was lower than that of PKUPH. Conclusion: The reported RUNX1-RUNX1T1 and WT1 transcript levels were different among laboratories for the same sample. Most of the participated laboratories reported highly consistent result with that of PKUPH. The relationship between laboratories of the different transcript levels may not be the same.

Immunohistochemical localization of sex hormone receptors in two Raillietina tapeworms.

Sex hormone receptors play critical roles in development and reproduction. However, it is not known whether they exist in Raillietina tapeworms, and if they do, whether they have a similar function to that in vertebrates. We examined the immunohistochemical distributions of androgen receptors (ARs), estrogen receptors (ERs), and progesterone receptors (PRs) in the tissues of two tapeworm species: Raillietina echinobothrida and Raillietina tetragona. Immunopositive ARs were found in the entire reproductive system of R. echinobothrida, including the testes, ovaries, and oocysts, and weakly immunopositive ERs and PRs were found in the testes, ovaries, and oocysts. Immunopositive ARs were also found throughout the entire reproductive system of R. tetragona, including the testes, ovaries, and oocysts, and weakly immunopositive ERs were in the testes and oocysts; the PRs were distributed in an immunonegative manner. The results show that androgens and their receptors play critical roles in reproductive system development in the two tapeworms. The immunoreactivity and tissue localizations of the sex hormone receptors suggest that, in both species, they have similar functions as in vertebrates, and modulate reproduction.

SUMOylation in Neurological Diseases.

Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases. In this review, we summarize the growing findings on protein sumoylation in neuronal function and dysfunction. It is essential to have a thorough understanding on the mechanism how sumoylation contributes to neurological diseases in developing efficient therapy for these diseases.

Sumoylation in Lens Differentiation and Pathogenesis.

Sumoylation, a post-translational modification discovered over a decade ago, turns out to be a very important regulatory mechanism mediating multiple cellular processes. Recent studies from our laboratory and others also revealed that it plays a crucial role in regulating both differentiation and pathogenesis of the ocular lens. This review will summarize these progresses.

Molecular Cloning and Developmental Expression Patterns of the Striatin Gene Encoding A Member of the Regulatory Subunits for the Protein Serine/Threonine Phosphatase-2A in Fish.

PURPOSE: The protein phosphatase-2A (PP-2A) is one of the most important serine/threonine phosphatases in eukaryotes. The holoenzyme of PP-2A consists of three subunits: a scaffold A subunit, a catalytic C subunit and a regulatory B subunit. While both A and C subunits are coded by two different genes, the B subunits exist in 26 or more isoforms which are encoded by at least 15 different genes. Previous studies have shown that besides regulating specific PP-2A activity, various B subunits may have other functions. To explore the possible roles of the regulatory subunits of PP-2A in vertebrate development, we have cloned the gene encoding goldfish striatin, a member of the B'" family regulatory subunits for PP-2A, and determined their tissue-specific and temporal expression patterns. METHODS: The cDNA cloning was conducted with RT-PCR-based RACE. The mRNA expression levels for the goldfish striatin were analyzed with RT-PCR. The expression levels of the striatin protein from goldfish were determined with Western blot analysis. The semi-quantitation of the mRNA and protein expression levels was conducted with the software of U-scanning. RESULTS: Our study revealed that the full length cDNA for striatin consists of 2965 bp coding for a deduced protein of 769 amino acids, which bears a very high level of amino acid sequence identity with the homolog protein from other species. The striatin mRNA is highly expressed in the kidney, to a less degree in brain, fin, muscle, liver, ovary and gill, and the lowest in testis and heart. Similar pattern of protein expression is detected in the above 9 tissues. During the development of goldfish, the striatin mRNA maintains a relatively high level at the 2-cell, multiple cell and blastula stages. Then, it drops down substantially at gastrula stage and fluctuates around this level in the next 8 different stages. At the protein level, the striatin maintained higher level from 2-cell to gastrula stages, then decreased at neurula and optic vesicle stages, and gradually increased again to peak at eye pigmentation stage, then slightly decreased in the next few stages of development. CONCLUSIONS: Our results suggest that the striatin may play an important role in regulating goldfish development and adult tissue homeostasis. While the former function may or may not occur through PP- 2A functions, the later function appears to occur via PP-2A activity.

Roles of SUMOylation in Heart Development and Cardiovascular Diseases.

Heart is an extremely important organ, and cardiovascular disorders emerge as primary life-threatening disease in human life. Aberrant post-translational modifications (PTMs) on cardiac proteins are closely correlated with pathological abnormalities in heart. SUMOylation, one of the most prevalent PTMs with thousands of substrates throughout the cell including critical subcellular organelles, has been shown to precisely finetune the cell survival and proliferation during heart development, and delicately control the function of mitochondrion and sarcoplasmic reticulum in physiological heart functioning. The silver lining is pathologically cardiacspecific SUMOylation being considered as target for cardiovascular disease intervention and treatment. Here, we summarize the recent progress in heart-specific functions of the SUMOylation pathway. In particular, we discuss the biological significance of SUMO conjugation/deconjugation during heart development, and in physiological cardiovascular health involving cardiac mitochondrial function, cardiac contractility, stress adaption and protein homeostasis. We also discuss the crosstalks between sumoylation and other post-translational modifications such as acetylation and ubiquitination. These crosstalks not only shed light to our understanding of the regulatory mechanisms on cardiovascular disorders but also contributes to their future therapy.

Regulation of CREB Functions by Phosphorylation and Sumoylation in Nervous and Visual Systems.

CREB is an ubiquitous transcription factor regulating diverse cellular responses. Its phosphorylation at S133 is an essential event for its activation in both nervous and visual systems. The activated CREB is implicated in the regulation of development, protection, learning, memory and plasticity in the nerve system. Moreover, sumoylation, an important post-translational modification of protein, plays a key role in sustaining CREB activation in the rat hippocampus in order to enhance the long-term memory and other aspects. In the visual system, although the CREB activation by phosphorylation at S133 is similar to that as observed in the nervous system, the role of CREB sumoylation remains to be explored. This review will discuss the aspects of CREB functions and their regulation by phosphorylation and sumoylation in both systems.

Cinnamon effectively inhibits the activity of leukemia stem cells.

Cinnamon is the main component of Sanyangxuedai, which is one of the effective traditional Chinese medicines for treating malignancies. Leukemia is a prevalent malignant disease that Sanyangxuedai has been used to treat. Although successful in several studies, there is a lack of solid evidence as to why Sanyangxuedai has an effect on leukemia, and little is known about the underlying mechanisms. In this study, the active ingredients of cinnamon were isolated, purified, and identified. The transwell transport pool formed with the Caco-2 cell model was used to filter the active ingredients of cinnamon by simulating the gastrointestinal barrier in vitro. Moreover, the cell morphology, cell cycle status, apoptosis status, and antigenic variation of the cell surface antigens were observed and measured in K562 cells after treatment with the active ingredients of cinnamon. Our results showed that 50-75 µM was a safe concentration of cinnamon extract for treatment of K562 cells for 72 h. The cinnamon extract caused growth inhibition of K562 cells. Cinnamon extract seemed to arrest the cells at the G1 stage and increased the apoptosis rate significantly. Interestingly, cinnamon extract treatment upregulated the expression of erythroid and myeloid differentiation antigens and downregulated that of the megakaryocytic differentiation antigens in a dose-dependent manner. Our findings indicate that cinnamon extract from Sanyangxuedai may be effective for treating leukemia.

Regulation of Eye Development by Protein Serine/Threonine Phosphatases-1 and -2A.

The protein serine/threonine phosphatases-1 and -2A are major cellular phosphatases, playing a fundamental role in organisms from prokaryotes to eukaryotes. They contribute to 90% dephosphorylation in eukaryote proteins. In the eye, both phosphatases are highly expressed and display important functions in regulating normal eye development. Moreover, they are implicated in pathogenesis through modulation of stress-induced apoptosis. Here we review the recent progresses on these aspects.

Influence of CYP3A5 genotypes on tacrolimus dose requirement: age and its pharmacological interaction with ABCB1 genetics in the Chinese paediatric liver transplantation.

AIM: The purpose of the study was to evaluate the impact of single nucleotide polymorphisms (SNPs) of Cytochrome P450 (CYP) 3A5 and adenosine triphosphate-binding cassette B1 (ABCB1) genotypes on TAC pharmacokinetics in Chinese paediatric patients. METHOD: A total of 136 Chinese paediatric liver recipients (R) and their donors (D) were divided into groups according to their CYP3A5 genotypes [expression of *1 allele: expressor (EX) or non-expressor (NEX)]. RESULT: Both recipient and donor CYP3A5*1 alleles had impacts on the TAC pharmacokinetics after liver transplantation. EX-R/EX-D recipients required a significantly higher TAC daily dose compared with NEX-R/NEX-D (0.24 ± 0.08 vs. 0.14 ± 0.06 mg/kg/day, p < 0.01). Age was also an independent factor on TAC requirement. Compared with EX-R/EX-D, non-expressor infants or recipients over 3-years old needed < 0.2 mg/kg/day. None of the ABCB1 SNPs (1236C>T, 2677G>A/T, 3435C>T) had an impact on TAC pharmacokinetics. However, EX-R/EX-D recipients bearing the ABCB1 1236-CC genotype required a much higher TAC dose than those without this genotype (0.23 vs. 0.18 mg/kg/day, p < 0.01), who required a similar TAC dose to that of NEX-R/NEX-D children. Furthermore, EX-R/EX-D with ABCB1 1236-CC recipients exhibited an markedly higher incidence of acute rejection and transplant-related infections clinically. CONCLUSION: CYP3A5 and ABCB1-1236 genotyping, in addition to recipient age, are necessary for establishing a more accurate TAC dosage regimen in paediatric liver recipients. We should be cautious regarding the treatment of paediatric recipients with both CYP3A5-expressor and ABCB1 1236-CC genotypes with TAC, as these patients are more susceptible to acute rejection and infection.

Auditory efferent dysfunction in normal-hearing chronic idiopathic tinnitus.

OBJECTIVE: To investigate the function of the auditory efferent system in patients with chronic idiopathic tinnitus, but normal pure-tone audiograms. METHODS: We studied 15 subjects with normal hearing that had experienced either unilateral or bilateral persistent tinnitus for at least 3 months. The ears of the 15 subjects were classified into tinnitus-positive-ear (TPE) and tinnitus-negative-ear (TNE) groups. The control-ear group (CE) comprised the ears of 15 subjects with normal hearing and no tinnitus. We measured different types of otoacoustic emissions (OAEs), including spontaneous (SOAEs), transient evoked (TEOAEs), and distortion product (DPOAEs). We also analyzed contralateral suppression of OAEs and auditory brainstem responses (ABRs). Data were compared among TPE, TNE, and CE groups. RESULTS: The data associated with cochlear mechanics, including the prevalence of SOAEs, the number of SOAE peaks, and the overall TEOAE responses in the absence of a contralateral stimulus, were not significantly different among the TPE, TNE, and CE groups. In the TPE group, contralateral stimuli failed to significantly suppress overall TEOAEs, and contralateral suppression of DPOAEs was significantly reduced over a limited frequency range. Furthermore, the TPE group showed prolonged latencies in waves III and V of ABRs. CONCLUSION: This study demonstrated that abnormal contralateral suppression of OAEs and ABRs indicated a dysfunction in the ipsilateral efferent medial olivocochlear system; this might play a role in normal-hearing tinnitus.

Photoconduction mechanism of oxygen sensitization in InN nanowires.

The photoconduction (PC) mechanism in indium nitride (InN) nanowires (NWs) has been investigated via environment-, temperature-, and power-dependent measurements. The adsorbed oxygen-induced modulation of the surface state is proposed to be the leading factor in the long lifetime or high gain transport and in sensitizing photocurrent generation in the InN NWs. The electron trapping effect by adsorbed oxygen can be verified by the increased activation energy from 33 ± 4 (in vacuum) to 58 ± 2 meV (in oxygen). The observed supralinear power dependence of photocurrent also suggests the presence of acceptor states that influence the carrier recombination behavior and compensate the thermal carriers in the InN NWs. The potential influence of native oxide on the molecule-sensitive PC in this nitride nanomaterial is also inferred.