Non-myeloablative allogeneic peripheral stem cell transplantation for multiple myeloma

Objective. To present an institution's 2-year experience of non-myeloablative allogeneic stem cell transplantation among Chinese patients. Design. Retrospective study. Setting. Bone marrow transplantation unit at a university hospital, Hong Kong. Patients. Ten patients with multiple myeloma who received non-myeloablative allogeneic stem cell transplantation between March 2000 and October 2002. Intervention. Fludarabine (90 mg/m 2) and total body irradiation (300 cGy) were given as conditioning regimens, followed by non-myeloablative allogeneic stem cell transplantation. Main outcome measures. Engraftment, regimen-related toxicity, treatment-related mortality (in the first 100 days), incidence of graft-versus-host disease, chimerism, disease response, and survival rate. Results. All 10 patients had active disease before transplantation. The donors were eight human leukocyte antigen-matched siblings, a mismatched sibling, and a matched daughter. Satisfactory engraftment before day 21 was achieved without early treatment-related mortality. Five patients developed full donor chimerism by day 28 and three other patients had 100% donor chimerism by day 100. Acute graft-versus-host disease developed in six patients (five with grade III and one with grade IV disease), and chronic graft-versus-host disease developed in eight patients (four with extensive disease). Complete remission and partial response were achieved in three and four patients, respectively. Three patients did not respond to treatment, and one case of relapse was observed. Only one patient, who had shown a partial response, received donor lymphocyte infusion; seven patients received thalidomide for graft-versus-host disease with or without graft-versus-myeloma effect. All patients were alive after a median follow-up of 1 year. Conclusion. Non-myeloablative allogeneic stem cell transplantation for multiple myeloma is effective, has low toxicity, and results in low treatment-related mortality. Studies of more cases with longer follow-up durations are required.published_or_final_versio

Non-gastric marginal zone B cell lymphoma: Clinicopathologic features and treatment results

The optimal treatment strategy and outcome of non-gastric marginal zone lymphoma (MZL) remains undefined. The role of rituximab and fludarabine in MZL has not been critically appraised and compared with conventional chemotherapy. We retrospectively analyzed 81 consecutive patients with non-gastric MZL (mucosa-associated lymphoid tissue lymphoma, n = 66; splenic MZL, n = 11; nodal MZL, n = 4). As a group, the treatment results were favorable, with an overall response rate of 87% and a complete response (CR) rate of 73%. The CR rate was similar for conventional chemotherapy, and rituximab- and fludarabine-containing regimens. However, the relapse rate was significantly decreased in rituximab- and fludarabine-containing regimens. The use of rituximab and fludarabine was associated with acceptable side effects. For splenic MZL, splenectomy was significantly associated with a superior CR rate. Early stage, good performance status, and low international prognostic index risk scores significantly impacted on CR rate and survivals. Rituximab and fludarabine were safe for non-gastric MZL and resulted in more durable remissions. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 21 Feb 201

Associations of hippocampal subfields in the progression of cognitive decline related to Parkinson's disease.

OBJECTIVE: Hippocampal atrophy has been associated with mild cognitive impairment (MCI) in Parkinson's disease (PD). However, literature on how hippocampal atrophy affects the pathophysiology of cognitive impairment in PD has been limited. Previous studies assessed the hippocampus as an entire entity instead of their individual subregions. We studied the progression of cognitive status in PD subjects over 18 in relation to hippocampal subfields atrophy. METHODS: 65 PD subjects were included. Using the MDS task force criteria, PD subjects were classified as either having no cognitive impairment (PD-NCI) or PD-MCI. We extended the study by investigating the hippocampal subfields atrophy patterns in those who converted from PD-NCI to PD-MCI (PD-converters) compared to those who remained cognitively stable (PD-stable) over 18 months. Freesurfer 6.0 was used to perform the automated segmentation of the hippocampus into thirteen subregions. RESULTS: PD-MCI showed lower baseline volumes in the left fimbria, right CA1, and right HATA; and lower global cognition scores compared to PD-NCI. Baseline right CA1 was also correlated with baseline attention. Over 18 months, decline in volumes of CA2-3 and episodic memory were also seen in PD-converters compared to PD-stable. Baseline volumes of GC-DG, right CA4, left parasubiculum, and left HATA were predictive of the conversion from PD-NCI to PD-MCI. CONCLUSION: The findings from this study add to the anatomical knowledge of hippocampal subregions in PD, allowing us to understand the unique functional contribution of each subfield. Structural changes in the hippocampus subfields could be early biomarkers to detect cognitive impairment in PD

Clinical management guidelines for osteoporosis in Hong Kong

The following guidelines provide a basis for the management of osteoporosis for the practising physician in Hong Kong. The guidelines have been complied by a working group that represents the specialties concerned with osteoporosis and summarise the current management of osteoporosis based on available published evidence and relevant local experience.published_or_final_versio

Graded magnonic index and spin wave fano resonances in magnetic structures: Excite, direct, capture

This is the author accepted manuscript. The final version is available from Pan Stanford via the DOI in this record Starting from the general topic and fundamentals of magnonics, we discuss and provide demonstrations of exciting new physics and technological opportunities associated with the graded magnonic index and spin wave Fano resonances, highlighting them as the next big thing in magnonics research.Engineering and Physical Sciences Research Council (EPSRC)European Union Horizon 202

Auditory temporal resolution and evoked responses to pulsed sounds for the Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis)

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Comparative Physiology A: Neuroethology, Sensory, Neural, and Behavioral Physiology 197 (2011): 1149-1158, doi:10.1007/s00359-011-0677-y.Temporal cues are important for some forms of auditory processing, such as echolocation. Among odontocetes (toothed whales, dolphins, and porpoises), it has been suggested that porpoises may have temporal processing abilities which differ from other odontocetes because of their relatively narrow auditory filters and longer duration echolocation signals. This study examined auditory temporal resolution in two Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis) using auditory evoked potentials (AEPs) to measure: (i) rate following responses and modulation rate transfer function for 100 kHz centered pulse sounds and (ii) hearing thresholds and response amplitudes generated by individual pulses of different durations. The animals followed pulses well at modulation rates up to 1250 Hz, after which response amplitudes declined until extinguished beyond 2500 Hz. The subjects had significantly better hearing thresholds for longer, narrower-band pulses similar to porpoise echolocation signals compared to brief, broadband sounds resembling dolphin clicks. Results indicate that the Yangtze finless porpoise follows individual acoustic signals at rates similar to other odontocetes tested. Relatively good sensitivity for longer duration, narrow-band signals suggests that finless porpoise hearing is well-suited to detect their unique echolocation signals.The work was supported by the Office of Naval Research, a WHOI Mellon Joint Initiatives Award , the Chinese National Natural Science Foundation (grant No: 30730018) and the Institute of Hydrobiology of the Chinese Academy of Sciences2012-09-1

Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons

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Cross-sectional survey of a sample of UK primary care dental professionals' experiences of sharps injuries and perception of access to occupational health support

Background: The 2013 Sharps Regulations were introduced to minimise the risk of sharps injuries and blood borne virus transmission throughout healthcare. Occupational health (OH) services are pivotal for helping employers implement these regulations. Despite this, no research has been conducted on the prevalence of sharps injuries, underreporting of injuries or access to OH among primary care dental professionals in the UK since 2013. Aim: To estimate the prevalence of sharps injuries, the level of underreporting and of self-reported access to an OH service both for the care of sharps injuries and for general health and wellbeing. Method: A cross-sectional survey was administered at the 2017 British Dental Association (BDA) Conference and Exhibition in Manchester, and at the 2017 BDA Scottish Conference and Exhibition in Glasgow. The survey covered questions relating to sharps injuries and OH support. Statistical analyses were conducted using SPSS Version 22 (IBM Corp., 2013). Results: A total of 796 delegates participated, of whom 166 (20.8%) had experienced a sharps injury in the past year and 58 (35%) did not report the incident. Of the participants, 190 (23.9%) reported no, or uncertain, access to OH support. Most respondents' practices had a sharps safety policy (771; 96.9%), but fewer (611; 76.8%) had received training on the prevention of sharps injuries and neither policy nor training were associated with incident reporting. Conclusion: Despite the introduction of the sharps regulations, sharps injuries and underreporting of injuries remain prevalent among those practising in primary dental care. Our results also suggest that there are significant shortfalls in OH support, at a time when changes to guidance on health clearance and management of BBV infected healthcare workers, in addition to sharps injury management, increase the need for such services

Genetic variation for sensitivity to a thyme monoterpene in associated plant species

Recent studies have shown that plant allelochemicals can have profound effects on the performance of associated species, such that plants with a history of co-existence with “chemical neighbour” plants perform better in their presence compared to naïve plants. This has cast new light on the complexity of plant–plant interactions and plant communities and has led to debates on whether plant communities are more co-evolved than traditionally thought. In order to determine whether plants may indeed evolve in response to other plants’ allelochemicals it is crucial to determine the presence of genetic variation for performance under the influence of specific allelochemicals and show that natural selection indeed operates on this variation. We studied the effect of the monoterpene carvacrol—a dominant compound in the essential oil of Thymus pulegioides—on three associated plant species originating from sites where thyme is either present or absent. We found the presence of genetic variation in both naïve and experienced populations for performance under the influence of the allelochemical but the response varied among naïve and experienced plant. Plants from experienced populations performed better than naïve plants on carvacrol soil and contained significantly more seed families with an adaptive response to carvacrol than naïve populations. This suggests that the presence of T. pulegioides can act as a selective agent on associated species, by favouring genotypes which perform best in the presence of its allelochemicals. The response to the thyme allelochemical varied from negative to neutral to positive among the species. The different responses within a species suggest that plant–plant interactions can evolve; this has implications for community dynamics and stability

Generation of a Cell Culture-Adapted Hepatitis C Virus with Longer Half Life at Physiological Temperature

BACKGROUND: We previously reported infectious HCV clones that contain the convenient reporters, green fluorescent protein (GFP) and Renilla luciferase (Rluc), in the NS5a-coding sequence. Although these viruses were useful in monitoring viral proliferation and screening of anti-HCV drugs, the infectivity and yield of the viruses were low. METHODOLOGY/PRINCIPAL FINDINGS: In order to obtain a highly efficient HCV cultivation system, we transfected Huh7.5.1 cells [1] with JFH 5a-GFP RNA and then cultivated cells for 20 days. We found a highly infectious HCV clone containing two cell culture-adapted mutations. Two cell culture-adapted mutations which were responsible for the increased viral infectivity were located in E2 and p7 protein coding regions. The viral titer of the variant was ∼100-fold higher than that of the parental virus. The mutation in the E2 protein increased the viability of virus at 37°C by acquiring prolonged interaction capability with a HCV receptor CD81. The wild-type and p7-mutated virus had a half-life of ∼2.5 to 3 hours at 37°C. In contrast, the half-life of viruses, which contained E2 mutation singly and combination with the p7 mutation, was 5 to 6 hours at 37°C. The mutation in the p7 protein, either singly or in combination with the E2 mutation, enhanced infectious virus production about 10-50-fold by facilitating an early step of virion production. CONCLUSION/SIGNIFICANCE: The mutation in the E2 protein generated by the culture system increases virion viability at 37°C. The adaptive mutation in the p7 protein facilitates an earlier stage of virus production, such as virus assembly and/or morphogenesis. These reporter-containing HCV viruses harboring adaptive mutations are useful in investigations of the viral life cycle and for developing anti-viral agents against HCV