Publications by authors named "Wing Cheung"

97 Publications

Fibrinolysis as a target to enhance osteoporotic fracture healing by vibration therapy in a metaphyseal fracture model.

Bone Joint Res 2021 Jan;10(1):41-50

Department of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Hong Kong.

Aims: Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing.

Methods: A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture.

Results: All rats achieved healing, and x-ray relative radiopacity for OVX-VT was significantly higher compared to OVX at week 2. Martius Scarlet Blue (MSB) staining revealed a significant decrease of fibrin content in the callus in OVX-VT compared with OVX on day 3 (p = 0.020). Mean tPA from muscle was significantly higher for OVX-VT compared to OVX (p = 0.020) on day 3. Mechanical testing revealed the mean energy to failure was significantly higher for OVX-VT at 37.6 N mm (SD 8.4) and 71.9 N mm (SD 30.7) compared with OVX at 5.76 N mm (SD 7.1) (p = 0.010) and 17.7 N mm (SD 11.5) (p = 0.030) at week 2 and week 6, respectively.

Conclusion: Metaphyseal fracture healing is enhanced by LMHFV, and one of the important molecular pathways it acts on is fibrinolysis. LMHFV is a promising intervention for osteoporotic metaphyseal fracture healing. The improved mechanical properties, acceleration of fracture healing, and safety justify its role into translation to future clinical studies. Cite this article:  2021;10(1):41-50.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1302/2046-3758.101.BJR-2020-0185.R1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7845465PMC
January 2021

The knowledge, perceptions, and attitudes toward vaccination in pregnancy, pertussis, and pertussis vaccination during pregnancy among pregnant women in Hong Kong.

J Obstet Gynaecol Res 2021 Jan 10. Epub 2021 Jan 10.

Department of Obstetrics and Gynaecology, Pamela Youde Nethersole Eastern Hospital, Chai Wan, Hong Kong SAR.

Aims: The Centre for Health Protection of Hong Kong has issued a recommendation on pertussis vaccination during pregnancy to protect infants against pertussis. This study aimed to explore the knowledge, perceptions, and attitudes toward pertussis vaccination during pregnancy among pregnant women in Hong Kong.

Methods: This was a cross-sectional study conducted over a 6-week period from August 17 to September 30 2019 among pregnant women in an obstetrics department in a regional public hospital in Hong Kong. Information on participants' demographics, medical, and immunization history, their knowledge, perception and attitudes, toward pertussis vaccination during pregnancy were gathered. Point-biserial correlation coefficients were used to determine correlation between variables.

Results: Only 112 (24.6%) women knew that pertussis vaccination can be given during pregnancy and 53 (11.6%) recognized that antenatal pertussis vaccination should be given in each pregnancy. Despite poor knowledge on the vaccination, over 80% of women showed an intention to receive pertussis vaccination during pregnancy. Fifty-two (71.3%) women expressed that recommendations by healthcare professionals may alter their decision on vaccination uptake. The score in the knowledge section and the perception to the vaccination positively correlated with the intention to be vaccinated. Those who were given advice by healthcare professionals were more likely to indicate an intention to receive the vaccination.

Conclusion: Pregnant women in Hong Kong are likely to accept antenatal pertussis vaccination despite the poor knowledge on vaccination in pregnancy and antenatal pertussis vaccination. Recommendations by healthcare professionals are a key factor affecting women's decision on vaccination uptake.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jog.14661DOI Listing
January 2021

Efficacy of low-magnitude high-frequency vibration (LMHFV) on musculoskeletal health of participants on wheelchair: a study protocol for a single-blinded randomised controlled study.

BMJ Open 2020 12 15;10(12):e038578. Epub 2020 Dec 15.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, New Territories, Hong Kong

Background: Osteoporosis is an age-related disease with progressive loss of bone, leading to fragile bone. It is one of the major health issues in older adults and causes medical, social and economic impacts globally. Patients with osteoporosis have high risk of osteoporotic fractures. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical intervention providing whole-body mechanical stimulation. Previous studies showed that LMHFV is beneficial to muscle strength, postural control, balancing ability, new bone formation, spinal bone mineral density (BMD) and blood circulation. During the LMHFV treatment, older adults need to stand upright on the platform for 20 min/day. However, some physically weak elderlies with poor musculoskeletal ability cannot stand for a long period. Therefore, the design of vibration platform is modified for the disabled patients to treat at sitting position and the efficacy of LMHFV on this group of elderlies will be verified. It is hypothesised that new design of LMHFV is beneficial to wheelchair users in terms of vertebral BMD, muscle health and musculoskeletal functions.

Methods: This study is a single-blinded randomised controlled trial to investigate the effect of LMHFV on vertebral BMD, muscle health, balancing ability and functional ability in wheelchair users (mainly on wheelchair for outdoor activities). Healthy elderlies aged 65 years or above with walking difficulties and using wheelchair are eligible. Exclusion criteria are those: (1) who cannot stand and walk independently, (2) who have vibration treatment before, (3) with malignancy, (4) with acute fractures or severe osteoarthritis, (5) with cardiovascular concern such as with pacemaker in situ, (6) with chronic inflammatory conditions known to affect muscle metabolism such as rheumatoid arthritis and (7) with high frequency of physical activities, such as participants who participated in regular exercise five times a week or more. Recruited participants will be randomised to either LMHFV or control group. Participant assigned to LMHFV group will receive LMHFV (35 Hz, 0.3g (g=gravitational acceleration), 20 min/day, at least three times/week) for 6 months. The primary outcome is BMD at the lumbar spine to be assessed by dual-energy X-ray absorptiometry that is clinically recommended for the diagnosis of osteoporosis. All primary and secondary outcome assessments for all groups will be performed in the investigators' institute at baseline and 6 months post treatment.

Discussion: This study aims to investigate the effects of LMHFV on wheelchair users. The findings of this study will help to confirm the efficacy of LMHFV on vertebral BMD, muscle health, balancing ability and functional outcomes in wheelchair using elderlies. LMHFV therapy is an intervention strategy that is easy to implement at the community healthcare level or individually at home that has previously been proven to reduce fall risk and muscle strength at the lower limb. The ultimate goal is to improve their bone and muscle quality of wheelchair users, as well as enhancing their quality of life.

Trial Registration Number: ClinicalTrials.gov (NCT04180267).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-038578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7745337PMC
December 2020

AmplifEYE assisted colonoscopy versus standard colonoscopy: A randomized controlled study.

J Gastroenterol Hepatol 2021 Feb 2;36(2):376-382. Epub 2020 Dec 2.

Department of Medicine, Queen Elizabeth Hospital, Hong Kong.

Background And Aim: AmplifEYE is a mucosal exposure device mounted to the tip of colonoscope to improve polyp or adenoma detection. We aim to compare the adenoma detection rates (ADR) of AmplifEYE-assisted colonoscopy (AC) with standard colonoscopy (SC).

Methods: We performed a randomized controlled trial involving patients aged 50 to 79 who underwent AC or SC in two centers. Procedures were performed by five experienced colonoscopists.

Results: Three hundred fifty-five patients were recruited, with 334 patients (170 AC and 164 SC) included into analysis. The ADR was numerically higher in AC (47.1%) versus SC (40.9%), P = 0.253. The polyp detection rate (PDR) in AC was 68.2% versus 54.3% in SC, P = 0.009, and serrated polyp detection rate (SDR) in AC was 37.6% versus 20.1% in SC, P < 0.001, both statistically significant higher in the study group. The mean cecal intubation time was shorter with AmplifEYE (8.0 min in AC vs 8.9 min in SC, P = 0.030), and there was no difference in pain score (3 in AC vs 4 in SC, P = 0.121).

Conclusions: AmplifEYE-assisted colonoscopy significantly improved the PDR and SDR, while the ADR was numerically higher in AC that did not reach statistical significance. Using the device resulted in shorter cecal intubation time and did not cause more pain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jgh.15331DOI Listing
February 2021

Uterine CD56 cell density and euploid miscarriage in women with a history of recurrent miscarriage: A clinical descriptive study.

Eur J Immunol 2021 Feb 30;51(2):487-489. Epub 2020 Oct 30.

Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, China.

In women with a history of recurrent miscarriage, the uterine CD56+ cell density in subjects with subsequent euploid miscarriage was significantly higher than those with subsequent aneuploid miscarriage. Both endometrial and embryonic factors should be investigated when interpreting uterine CD56+ cell density results relating to recurrent miscarriage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eji.202048868DOI Listing
February 2021

Enhancement of osteoporotic fracture healing by vibration treatment: The role of osteocytes.

Injury 2020 May 21. Epub 2020 May 21.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, China.

The prevalence of osteoporotic fracture is high due to global aging problem. Delayed and impaired healing in osteoporotic fractures increase the socioeconomic burden significantly. Through intensive animal and clinical research in recent years, the pathogenesis of osteoporotic fracture healing is unveiled, including decreased inflammatory response, reduced mesenchymal stem cells and deteriorated angiogenesis, etc. The enhancement of osteoporotic fracture healing is important in shortening hospitalization, thus reducing related complications. Mechanical stimulation is currently the most well-accepted approach for rehabilitation of osteoporotic fracture patients. Some new interventions providing mechanical signals were explored extensively in recent years, including vibration treatment, and osteoporotic fracture healing was found to respond very well to these signals. Vibration treatment could accelerate osteoporotic fracture healing with improved callus formation, mineralization and remodeling. However, the mechanism of how osteoporotic fracture bones sense mechanical signals and relay to bone formation remains unanswered. Osteocytes are the most abundant cells in bone tissues. Cumulative evidence confirm that osteocyte is a type of mechanosensory cell and shows altered morphology and reduced cell density during aging. Meanwhile, osteocytes serve as endocrine cells to regulate bone and mineral homeostasis. However, the contribution of osteocytes in osteoporotic fracture healing is largely unknown. A recent in vivo study was conducted to examine the morphological and functional changes of osteocytes after vibration treatment in an osteoporotic metaphyseal fracture rat model. The findings demonstrated that vibration treatment induced significant outgrowth of canaliculi and altered expression of various proteins (E11, DMP1, FGF23 and sclerostin), particularly osteocyte-specific dentin matrix protein 1 (DMP1) which was greatly increased. DMP1 may play a major role in relaying mechanical signals to bone formation, which may require further experiments to consolidate. Most importantly, vibration treatment significantly increased the mineralization and accelerated the osteoporotic fracture healing in metaphyseal fracture model. In summary, osteocyte is the major cell type to sense mechanical signals and facilitate downstream healing in osteoporotic fracture bone. Vibration treatment has good potential to be translated for clinical application to benefit osteoporotic fracture patients, while randomized controlled trials are required to validate its efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.injury.2020.05.020DOI Listing
May 2020

How much do we know about the role of osteocytes in different phases of fracture healing? A systematic review.

J Orthop Translat 2020 Mar 8;21:111-121. Epub 2019 Aug 8.

Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, PR China.

Background: Although emerging studies have provided evidence that osteocytes are actively involved in fracture healing, there is a general lack of a detailed understanding of the mechanistic pathway, cellular events and expression of markers at different phases of healing.

Methods: This systematic review describes the role of osteocytes in fracture healing from early to late phase. Literature search was performed in PubMed and Embase. Original animal and clinical studies with available English full-text were included. Information was retrieved from the selected studies.

Results: A total of 23 articles were selected in this systematic review. Most of the studies investigated changes of various genes and proteins expression patterns related to osteocytes. Several studies have described a constant expression of osteocyte-specific marker genes throughout the fracture healing cascade followed by decline phase with the progress of healing, denoting the important physiological role of the osteocyte and the osteocyte lacuno-canalicular network in fracture healing. The reports of various markers suggested that osteocytes could trigger coordinated bone healing responses from cell death and expression of proinflammatory markers cyclooxygenase-2 and interleukin 6 at early phase of fracture healing. This is followed by the expression of growth factors bone morphogenetic protein-2 and cysteine-rich angiogenic inducer 61 that matched with the neo-angiogenesis, chondrogenesis and callus formation during the intermediate phase. Tightly controlled regulation of osteocyte-specific markers E11/Podoplanin (E11), dentin matrix protein 1 and sclerostin modulate and promote osteogenesis, mineralisation and remodelling across different phases of fracture healing. Stabilised fixation was associated with the finding of higher number of osteocytes with little detectable bone morphogenetic proteins expressions in osteocytes. Sclerostin-antibody treatment was found to result in improvement in bone mass, bone strength and mineralisation.

Conclusion: To further illustrate the function of osteocytes, additional longitudinal studies with appropriate clinically relevant model to study osteoporotic fractures are crucial. Future investigations on the morphological changes of osteocyte lacuno-canalicular network during healing, osteocyte-mediated signalling molecules in the transforming growth factor-beta-Smad3 pathway, perilacunar remodelling, type of fixation and putative biomarkers to monitor fracture healing are highly desirable to bridge the current gaps of knowledge.The translational potential of this article: This systematic review provides an up-to-date chronological overview and highlights the osteocyte-regulated events at gene, protein, cellular and tissue levels throughout the fracture healing cascade, with the hope of informing and developing potential new therapeutic strategies that could improve the timing and quality of fracture healing in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jot.2019.07.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7152791PMC
March 2020

Early transient suppression of immune checkpoint proteins T-cell immunoglobulin mucin-3 and programmed cell death-1 in peripheral blood lymphocytes after blastocyst transfer is associated with successful implantation.

Fertil Steril 2020 Aug 18;114(2):426-435. Epub 2020 Mar 18.

Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, People's Republic of China. Electronic address:

Objective: To compare the changing peripheral levels of immune checkpoint proteins T-cell immunoglobulin mucin-3 (Tim-3)/galectin-9 (Gal-9), and programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) over a 9-day period after blastocyst transfer between women who did and did not conceive.

Design: Prospective observational study.

Setting: University teaching hospital.

Patients(s): Fifty-one infertile women undergoing day-5 blastocyst transfer.

Intervention(s): Serial blood samples obtained on the day of embryo transfer (ET), and 3, 6, and 9 days afterward for measurement of membranous Tim-3 and PD-1 expression on various peripheral lymphocytes by flow cytometry, and serum concentrations of ligands Gal-9 and PD-L1 by ELISA.

Main Outcome Measure(s): Membranous Tim-3 and PD-1 expression on lymphocytes and serum Gal-9 and PD-L1 concentrations and comparison of results between pregnant and nonpregnant women.

Result(s): In women who conceived, the measurements exhibited three different types of response: [1] a transient and statistically significant reduction of Tim-3NK-like T cells, Tim-3/PD-1CD8 T cells, and Tim-3/PD-1CD4 T cells that returned back to baseline level 9 days after ET; [2] a reduction followed by steady increase to above baseline level on day 9 (Tim-3CD56NK cells); [3] a steady increase in expression after ET to reach a level statistically significantly higher than that of the baseline by day 9 (Tim-3CD56NK cells). Women who did not conceive showed no statistically significant fluctuation in any of the parameters measured across the four time pointswith exception of increased Tim-3 expression on NK cells on day 9.

Conclusion(s): Successful blastocyst implantation is associated with a reduction of Tim-3 and PD-1 expression in peripheral lymphocytes on days 3 and 6 that is no longer apparent on day 9.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2019.12.022DOI Listing
August 2020

Role of Ultrasound in Low Back Pain: A Review.

Ultrasound Med Biol 2020 Jun 17;46(6):1344-1358. Epub 2020 Mar 17.

Department of Electrical and Electronic Engineering, Biomedical Engineering Programme, University of Hong Kong, Pokfulam, SAR, China.

Low back pain is one of most common musculoskeletal disorders around the world. One major problem clinicians face is the lack of objective assessment modalities. Computed tomography and magnetic resonance imaging are commonly utilized but are unable to clearly distinguish patients with low back pain from healthy patients with respect to abnormalities. The reason may be the anisotropic nature of muscles, which is altered in function, and the scans provide only structural assessment. In view of this, ultrasound may be helpful in understanding the disease as it is performed in real-time and comprises different modes that measure thickness, blood flow and stiffness. By the use of ultrasound, patients with low back pain have been found to differ from healthy patients with respect to the thickness and stiffness of the transversus abdominis, thoracolumbar fascia and multifidus. The study results are currently still not conclusive, and further study is necessary to validate. Future work should focus on quantitative assessment of these tissues to provide textural, structural, hemodynamic and mechanical studies of low back pain. This review highlights the current understanding of how medical ultrasound has been used for diagnosis and study of low back pain and discusses potential new applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ultrasmedbio.2020.02.004DOI Listing
June 2020

Association between chronic endometritis and uterine natural killer cell density in women with recurrent miscarriage: clinical implications.

J Obstet Gynaecol Res 2020 Jun 18;46(6):858-863. Epub 2020 Mar 18.

Assisted Reproductive Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Aim: This aim of this study was to determine the association between uterine natural killer (uNK) cell density and chronic endometritis (CE).

Methods: Endometrial biopsies from 135 women with recurrent miscarriage were obtained precisely 7 days after luteinizing hormone surge in natural cycles. Endometrial sections were immunostained for CD56 for uNK cells and CD138 for plasma cells, respectively. Uterine NK cell counting was performed according to a standardized protocol and results were expressed as percentage of CD56+ cells/ total stromal cells. High uNK cell density was defined as >4.5% and CE was diagnosed when the plasma cell density > 5.15 cells/ 10 mm .

Results: The uNK cells density in women with CE (median, 5.1%; range, 3.4-8.8%) was significantly (P < 0.05) higher than that of those without CE (median, 3.8%; range, 1.2%-7.3%). The prevalence of high uNK cell density in women with CE (11/29, 37.9%) was significantly (P < 0.05) higher than that of women without CE (8/106, 7.5%).

Conclusion: To conclude, there was a significant association between high uNK cell density and CE. In women with high uNK cell density, plasma cell should be examined to determine if the underlying cause is associated with CE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jog.14250DOI Listing
June 2020

Tumor lysis syndrome in childhood malignancies.

Drugs Context 2020 25;9. Epub 2020 Feb 25.

Department of Pediatrics, The University of Calgary, Alberta Children's Hospital, Calgary, AB, Canada.

Background: Tumor lysis syndrome (TLS) is the most common life-threatening oncological emergency encountered by physicians treating children with lymphoproliferative malignancies. Healthcare providers should be aware of the condition in order to prevent occurrence and prompt timely management to avoid severe consequences.

Objective: To provide an update on the current understanding, evaluation, and management of tumor lysis syndrome in childhood malignancies.

Methods: A PubMed search was performed in Clinical Queries using the keywords 'tumor lysis syndrome' and 'malignancies' with Category limited to clinical trials and reviews for ages from birth to 18 years.

Results: There were 22 clinical trials and 37 reviews under the search criteria. TLS is characterized by acute electrolyte and metabolic disturbances resulting from massive and abrupt release of cellular contents into the circulation due to breakdown of tumor cells. If left untreated, it can lead to multiorgan compromise and eventually death. Apart from close monitoring and medical therapies, early recognition of risk factors for development of TLS is also necessary for successful management.

Conclusions: Prophylactic measures to patients at risk of TLS include aggressive fluid management and judicious use of diuretics and hypouricemic agents. Both allopurinol and urate oxidase are effective in reducing serum uric acid. Allopurinol should be used as prophylaxis in low-risk cases while urate oxidase should be used as treatment in intermediate to high-risk cases. There is no evidence on better drug of choice among different urate oxidases. The routine use of diuretics and urine alkalinization are not recommended. Correction of electrolytes and use of renal replacement therapy may also be required during treatment of TLS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7573/dic.2019-8-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048108PMC
February 2020

Vibration and β-hydroxy-β-methylbutyrate treatment suppresses intramuscular fat infiltration and adipogenic differentiation in sarcopenic mice.

J Cachexia Sarcopenia Muscle 2020 04 28;11(2):564-577. Epub 2020 Jan 28.

Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong SAR, The People's Republic of China.

Background: Sarcopenia is an aging-induced deterioration of skeletal muscle mass and function. Low-magnitude high-frequency vibration (LMHFV) was shown to improve muscle functions and β-hydroxy-β-methylbutyrate (HMB) to increase muscle mass and strength. Muscle-derived stem cells (MDSCs) are progenitor cells important for muscle regeneration. We hypothesized that LMHFV and HMB could retard sarcopenia by reducing fat infiltration through inhibiting adipogenesis in MDSCs.

Methods: Senescence-accelerated mouse P8 male mice were randomized into control (CTL), HMB, LMHFV (VIB), and combined (COM) groups. Interventions started at age of month 7 and assessed at 1, 2, and 3 months post-intervention by densitometry, histology, and functional tests. In vitro, MDSCs isolated from gastrocnemius of senescence-accelerated mouse P8 mice were characterized, randomized into CTL, VIB, HMB, and COM groups, and assessed by oil red O staining, mRNA, and protein expression.

Results: At 2 months post-intervention, percentage lean mass of HMB, VIB, and COM groups were significantly higher than CTL group. Twitch, tetanic, and specific tetanic forces of COM group were higher, while specific twitch force of both VIB and COM groups were higher. Grip strength of HMB, VIB, and COM groups were higher. Histologically, both VIB and COM groups presented lower oil red O area than CTL group. Type I muscle fibre in CTL group was higher than HMB, VIB, and COM groups. MDSC were detected in situ by immunofluorescence stain with stem cell antigen-1 signals confirmed with higher β-catenin expression in the COM group. The observations were also confirmed in vitro, MDSCs in the HMB, VIB, and COM groups presented lower adipogenesis vs. the CTL group. β-Catenin mRNA and protein expressions were lower in the CTL group while their relationship was further validated through β-catenin knock-down approach.

Conclusions: Our results showed that combined LMHFV and HMB interventions enhanced muscle strength and decreased percentage fat mass and intramuscular fat infiltration as compared with either treatment alone. Additive effect of LMHFV and HMB was demonstrated in β-catenin expression than either treatment in MDSCs and altered cell fate from adipogenesis to myogenesis, leading to inhibition of intramuscular lipid accumulation. Wnt/β-catenin signalling pathway was found to be the predominant regulatory mechanism through which LMHFV and HMB combined treatment suppressed MDSCs adipogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcsm.12535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113529PMC
April 2020

2020 Young Investigator Award Winner: Age- and Sex-related Normative Value of Whole-body Sagittal Alignment Based on 584 Asymptomatic Chinese Adult Population From Age 20 to 89.

Spine (Phila Pa 1976) 2020 Jan;45(2):79-87

SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

Study Design: A cross-sectional radiographic study.

Objective: The aim of this study was to establish the age- and sex-related normative values of whole-body sagittal alignment in asymptomatic Chinese adult population, and to investigate the changes and possible associated compensation mechanisms across age groups.

Summary Of Background Data: Previous studies have reported normative data for sagittal spinal alignment in asymptomatic adults. However, there was a lack of comprehensive investigation on age- and sex-related normative values of whole-body sagittal alignment.

Methods: A total of 584 asymptomatic Chinese adults aged 20 to 89 years were recruited. Subjects were grouped according to age and sex. Whole-body standing radiographs were acquired for evaluating sagittal alignment from spine to lower limb. Comparisons of sagittal parameters between sex in different age groups were performed by independent t test. Pearson correlation analysis was used to determine relationships between each parameter.

Results: Mean values of each sagittal parameter were presented based on age and sex. Thoracic kyphosis showed steady increasing trend while lumbar lordosis gradual decrease in both sexes. Pelvic tilt (PT) in males is greater than in females across all age groups with age-related gradual increase. There were significant differences between males and females from 20 to 60 years in terms of KneeFlex angle (KA) and AnkleFlex angle, but the differences were not significant after 60s. T1 pelvic angle (TPA) was significantly correlated with spinal, pelvic and lower-limb alignment. The older group (≥50 years) had a stronger correlation of TPA with PT and KA, whereas the younger (<50 years) had stronger correlation with TK.

Conclusion: This study presented a comprehensive study of whole-body sagittal alignment based on a large asymptomatic population, which could serve as an age- and sex-specific reference value for spine surgeons when planning for correction surgery. Age can influence the recruitment of compensation mechanism that involves more pelvic and lower limb mechanisms for elderly people.

Level Of Evidence: 3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/BRS.0000000000003187DOI Listing
January 2020

Abnormal Osteoblastic Response to Leptin in Patients with Adolescent Idiopathic Scoliosis.

Sci Rep 2019 11 20;9(1):17128. Epub 2019 Nov 20.

SH Ho Scoliosis Research Laboratory, Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, The Prince of Wales Hospital, Hong Kong, SAR, China.

Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional structural deformity of the spine with unknown etiology. Although leptin has been postulated as one of the etiologic factors in AIS, its effects on osteoblastic activity remain unknown. Herein, we conducted this study to investigate whether there are abnormal functional responses to leptin and abnormal expression of leptin receptor in AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 12 severe AIS girls and 6 non-AIS controls. The osteoblasts were exposed to different concentrations of leptin (0, 10, 100, 1000 ng/mL). The effects of leptin on cell proliferation, differentiation and mineralization were determined. Protein expressions of leptin receptor (LEP-R) under basal and osteogenic conditions were also evaluated by Western blot. Our results showed that leptin significantly stimulated osteoblasts from non-AIS subjects to proliferate, differentiate and mineralized. However, in the AIS group, the stimulatory effects of leptin on cell proliferation, differentiation, and mineralization were not observed. In addition, no statistically significant difference in the expression of leptin receptor under both basal and osteogenic conditions was found between AIS and control group. In conclusion, these findings might help to explain the low bone mass and deranged bone quality that is clinically associated with AIS girls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-53757-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868007PMC
November 2019

Muscle-generated BDNF is a sexually dimorphic myokine that controls metabolic flexibility.

Sci Signal 2019 08 13;12(594). Epub 2019 Aug 13.

School of Biological Sciences, The University of Hong Kong, 6N01 Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong.

The ability of skeletal muscle to switch between lipid and glucose oxidation for ATP production during metabolic stress is pivotal for maintaining systemic energy homeostasis, and dysregulation of this metabolic flexibility is a dominant cause of several metabolic disorders. However, the molecular mechanism that governs fuel selection in muscle is not well understood. Here, we report that brain-derived neurotrophic factor (BDNF) is a fasting-induced myokine that controls metabolic reprograming through the AMPK/CREB/PGC-1α pathway in female mice. Female mice with a muscle-specific deficiency in BDNF (MBKO mice) were unable to switch the predominant fuel source from carbohydrates to fatty acids during fasting, which reduced ATP production in muscle. Fasting-induced muscle atrophy was also compromised in female MBKO mice, likely a result of autophagy inhibition. These mutant mice displayed myofiber necrosis, weaker muscle strength, reduced locomotion, and muscle-specific insulin resistance. Together, our results show that muscle-derived BDNF facilitates metabolic adaption during nutrient scarcity in a gender-specific manner and that insufficient BDNF production in skeletal muscle promotes the development of metabolic myopathies and insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scisignal.aau1468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219567PMC
August 2019

A comparison of uterine natural killer cell density in the peri-implantation period between natural cycles and hormone replacement therapy cycles.

Am J Reprod Immunol 2019 09 25;82(3):e13156. Epub 2019 Jun 25.

Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong.

Problem: A reference range for uterine natural killer (uNK) cell density in the peri-implantation period has recently been established in natural cycles. However, it is uncertain whether the results can be applied to hormonal replacement therapy (HRT) cycles, used increasingly in frozen-thaw embryo replacement cycles and which is known to be capable of supporting implantation.

Method Of Study: A total of 183 women from two IVF centers participated in this study, including 75 women in natural cycles and 108 women in HRT cycles. All endometrial biopsies were collected precisely on the putative day of embryo implantation, namely 7 days after LH surge (LH+7) of the natural cycles or 5 days after initiation of progesterone (P+5) of the HRT cycles. Endometrial sections were immunostained for CD56 for uNK cells. Cell counting was performed by a standardized protocol, and results were expressed as percentage of positive uNK cells/total stromal cells.

Results: There was no significant difference (P > 0.05) in uNK cell density between natural cycles (median 2.28%, range 0.99%-4.78%) and HRT cycles (median 2.55%, range 0.69%-5.02%) in women undergoing IVF-ET treatment on the putative day of blastocyst transfer. Using reference range from 1.2% to 4.5% for uNK cell density, there was no significant difference (P > 0.05) in high uNK cell density proportion between natural cycles (8%, 6/75) and HRT cycles (10.2%, 11/108).

Conclusion: The results indicated that the reference range for uNK cell density derived from natural cycles may apply to HRT cycles.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aji.13156DOI Listing
September 2019

Endometrial Vascularization Characterized by Optical Coherence Tomography and Immunohistochemistry in Women Undergoing In Vitro Fertilization-Embryo Transfer Treatment.

Medicina (Kaunas) 2019 Mar 27;55(4). Epub 2019 Mar 27.

Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong.

Background And Objective: Endometrial angiogenesis is a prerequisite for successful pregnancy. Optical coherence tomography (OCT) is a non-invasive physically optical imaging technique widely used in ophthalmology and cardiology. However, there is no study using OCT to evaluate endometrium. The aim of this study was to use OCT and traditionally histological methods to investigate endometrial vascularization in women undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment and to determine the association with the pregnancy outcome.

Methods: A total of 47 women were included in this study. OCT was used to assess endometrial vascularization by determining the high signal areas precisely on the seventh day after luteinizing hormone surge in non-conception natural cycles. Endometrial biopsies were obtained following OCT and immunohistochemistry was used to determine micro vessel and expression of vascular endothelial growth factor-A (VEGF-A) in the luminal epithelium, glandular epithelium and stroma, separately. Micro vessel counting was performed and the result was expressed as micro vessel density (MVD). A semi-quantitative H-score was used to determine the staining intensity of VEGF-A.

Results: In women who successfully conceived after embryo transfer, the proportion of extensive high signal area in the uterine body detected by OCT (80%, 8/10), MVD (median number of micro vessels/mm² of 10, range 4⁻17) and stromal expression of VEGF-A (median H-score of 189, range 72⁻395) were found to be significantly higher than those of women who did not conceive after embryo transfer in the subsequent IVF-ET treatment (OCT: 30%, 3/10; MVD: median number of micro vessels/mm² of 7, range 4⁻10; VEGF-A: median H-score of 125, range 86⁻299, respectively). In addition, a significantly higher stromal expression of VEGF-A (median H-score of 196, range 84⁻395) and MVD (median number of micro vessels/mm of 9, range 5⁻16) was found in women with extensive high signal area in uterine body, compared to those with focal or no high signal area (stromal VEGF-A: median H-score of 135, range 92⁻302; MVD: number of micro vessels/mm of 6, range 4-11).

Conclusions: Both immunohistochemistry and OCT demonstrated significant difference in vascularization of the peri-implantation endometrium between subjects who did and did not conceive after IVF-ET treatment. Our findings also suggest OCT appears to be a promising non-invasive or minimally invasive alternative to study endometrial vascularity in women with reproductive failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/medicina55040081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524031PMC
March 2019

Identification of molecular biomarkers for the diagnosis of gastric cancer and lymph-node metastasis.

Gastroenterol Rep (Oxf) 2019 Feb 13;7(1):57-66. Epub 2018 Aug 13.

Department of Gastric Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, P.R. China.

Background And Objective: Biomarkers are important tools for prompt diagnosis of cancer. This study aimed to identify reliable biomarkers for clinical applications in the diagnosis of gastric cancer and lymph-node (LN) metastasis.

Methods: Between 1 December 2014 and 31 December 2015, we prospectively collected samples of gastric-cancer tissues, corresponding matched-pair normal gastric mucosa, and their peri-gastric metastatic and non-metastatic LNs to identify quantitatively reliable genes using quantitative real-time polymerase chain reaction. Relative quantity (RQ) was used to calculate the mRNA expression levels of our target genes. Statistics were calculated using one-way analysis of variance (ANOVA) and Tukey's multiple comparison test. Analytical graphs were plotted using GraphPad Prism.

Results: Of nine assessed genes, the mRNA levels of inhibin beta A () and secreted phosphoprotein 1 () were most consistently highly expressed in tumor tissues by 15.4- and 15.6-fold, respectively, as compared with normal tissues ( < 0.001), with 91.3% sensitivity and 95.7% specificity (receiver operating characteristic [ROC] curve area = 0.974) for the former and 82.6% sensitivity and 87.0% specificity (ROC curve area = 0.924) for the latter. Further analysis revealed no differentiating significance of mRNA expression between metastatic and non-metastatic LNs ( = 0.470). In contrast, the mRNA level was up-regulated 4.1-fold in metastatic LNs ( < 0.001), with 80.0% sensitivity and 81.5% specificity (ROC curve area = 0.857), and was also able to successfully differentiate between more severe disease conditions, T3 and T4 ( = 0.003), M0 and M1 ( = 0.043) and different histological variants (intestinal type vs diffuse type,  = 0.019).

Conclusions: Our results showed that was the most optimally reliable biomarker for diagnosing gastric cancer and LN metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gastro/goy023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375354PMC
February 2019

Gelsemium poisoning mediated by the non-toxic plant Cassytha filiformis parasitizing Gelsemium elegans.

Toxicon 2018 Nov 28;154:42-49. Epub 2018 Sep 28.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Kowloon, Hong Kong. Electronic address:

Introduction: Gelsemium poisoning is caused by consumption of the deadly Gelsemium species such as Gelsemium elegans, leading to significant gastrointestinal, neurological and cardio-respiratory toxicities. In 2011 (Cluster 1) and 2012 (Cluster 2), the authors encountered two clusters of gelsemium poisoning after consumption of the non-toxic parasitic plant Cassytha filiformis. The current study aims to examine the mechanism of gelsemium poisoning mediated by a benign parasitic plant.

Methods: Qualitative analysis of toxic gelsemium alkaloids using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed on the herbal and urine samples from both clusters to confirm exposure. Morphological examination, qualitative analysis of aporphine alkaloids using liquid chromatography-ion trap-time of flight mass spectrometry (LC-IT-TOF/MS) and Sanger sequencing were performed on the plant sample from Cluster 2 to confirm its identity. A field study was conducted in local countryside and C. filiformis was collected for histological, LC-MS/MS and LC-IT-TOF/MS analyses to study its interaction with G. elegans.

Results: Gelsemium alkaloids that are not naturally present in C. filiformis were detected in the patients' herbal and urine samples. Misidentification and contamination with G. elegans during the preparation process were excluded by morphological examination of the plant sample from Cluster 2. Its identity as C. filiformis was verified with LC-IT-TOF/MS and molecular analyses. Histological, LC-MS/MS and LC-IT-TOF/MS analyses of C. filiformis collected during the field study confirmed that its haustoria penetrated the vascular bundles of G. elegans and absorbed its gelsemium toxins.

Conclusions: The non-toxic plant C. filiformis absorbed toxic gelsemium alkaloids from its host, G. elegans, and led to gelsemium poisoning in our patients. Our study provides new insights into the toxicology of such plants. Benign parasitic plants may lead to potentially life-threatening poisoning if it parasitizes toxic hosts and absorbs their phytotoxins. The public awareness of risks associated with the use of these medicinal parasitic plants should be raised.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.toxicon.2018.09.009DOI Listing
November 2018

Multichromatic TTF staining characterizes cartilage matrix in osteoarthritis and bone development.

Histol Histopathol 2019 Mar 20;34(3):275-286. Epub 2018 Sep 20.

Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.

Various histological staining methods have been explored to detect the joint lesions in osteoarthritis (OA), but these histological stains cannot comprehensively present the comparatively complex structures of articular cartilage in knee OA. In addition, no integrated histological staining method can be used to evaluate efficiently both the subzone region and matrix composition in cartilage containing tissues. Therefore, in this study, a novel multichromatic staining method termed TTF staining, using Toluidine Blue (T), Tartrazine (T) and Fast Green (F) sequential combined staining for histological analysis, has been exploited to characterize the changes of matrix components and contents in cartilage during OA and in the bone development. This specific TTF staining profile can be used to differentiate the major compartments of knee joint region, including the synovium, meniscus, multiple subzones of cartilage and subchondral bone. An anterior cruciate ligament transection induced OA model in rat has been established to profoundly present the alterations of glycosaminoglycans in cartilage degeneration by TTF staining profile. The changes of TTF staining profile in the chondrification and ossification centers of the postnatal rat knee joint indicate the developmental features of cartilage matrix during the growth of bone. In summary, we have developed an effective histological staining method that enables us to identify the subzones of cartilage in detail and to define the matrix features of bone development. Therefore, finally using this new TTF staining method may help us to exploit a histopathological grading system to assess cartilage lesions in clinical disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14670/HH-18-044DOI Listing
March 2019

Territory-wide population-based study of chronic hepatitis C infection and implications for hepatitis elimination in Hong Kong.

Liver Int 2018 11 30;38(11):1911-1919. Epub 2018 Jul 30.

Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.

Background: To study the epidemiology of chronic hepatitis C virus infection in Hong Kong and to estimate the service gap for achieving the WHO hepatitis elimination targets of attaining a diagnosis rate of 90%, treatment rate of 80% and 65% reduction in mortality rate by 2030.

Methods: From January 2005 to March 2017, patients who were tested positive for anti-HCV were retrospectively retrieved from all public hospitals in Hong Kong. The epidemiological data of 15 participating hospitals were analysed.

Results: A total of 11 309 anti-HCV+ patients were identified and the estimated diagnosis rate was 50.9%. Our HCV-infected patients were ageing (median age 59). The all-cause mortality rate increased from 26.2 to 54.8 per 1000 person-years over the last decade. Our estimated treatment rate was 12.4%. Among the treated patients, 93.6% had received pegylated interferon/ribavirin (Peg-IFN/RBV) but only 10.8% had received interferon-free direct-acting antivirals (DAAs). In a cohort of 1533 patients, 39% already had advanced liver fibrosis or cirrhosis. The sustained virological response rate for Peg-IFN/RBV and DAAs were 74.8% and 97.2% respectively. However, more than 70% of patients were not subjected to interferon treatment for various reasons. Patients who achieved SVR were associated with a significantly lower risk of HCC (4.7% vs 9.6%, P = 0.005) and death (1.7% vs 23.8%, P < 0.001).

Conclusion: Our diagnosis rate, treatment rate and mortality rate reduction were still low, particularly the Peg-IFN outcomes, making it difficult to meet the WHO hepatitis elimination targets. A more generalized use of DAAs is urgently needed to improve the situation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/liv.13926DOI Listing
November 2018

Genetic diagnosis of CADASIL in three Hong Kong Chinese patients: A novel mutation within the intracellular domain of NOTCH3.

J Clin Neurosci 2018 Oct 3;56:95-100. Epub 2018 Jul 3.

Kowloon West Cluster Laboratory Genetic Service, Chemical Pathology Laboratory, Department of Pathology, Princess Margaret Hospital, Hong Kong Special Administrative Region. Electronic address:

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an adult onset hereditary stroke syndrome characterized by recurrent stroke and progressive cognitive impairment caused by NOTCH3 mutations. We report here the clinical and molecular findings of three unrelated Hong Kong Chinese families with CADASIL syndrome. Sanger sequencing of genomic DNA revealed a novel heterozygous variant NM_000435.2(NOTCH3):c.[5903_5904insATAA];[5903_5904=] NP_000426.2:p.(Asp1969);(Asp1969=) and two previously reported heterozygous mutations NM_000435.2(NOTCH3):c.[328C>T];[328C=] NP_000426.2:p.[(Arg110Cys)];[(Arg110=)] and NM_000435.2(NOTCH3):c.[580T>A];[580T=] NP_000426.2:p.(Cys194Ser);(Cys194=) in the three families respectively. Molecular basis of CADASIL in these three patients were further established. Genetic analysis provides a reliable method for confirming the diagnosis of CADASIL and enables proper genetic counseling and cascade testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2018.06.050DOI Listing
October 2018

Everolimus dosing recommendations for tuberous sclerosis complex-associated refractory seizures.

Epilepsia 2018 06 4;59(6):1188-1197. Epub 2018 May 4.

New York University Comprehensive Epilepsy Center, New York, NY, USA.

Objective: The present analysis examined the exposure-response relationship by means of the predose everolimus concentration (C ) and the seizure response in patients with tuberous sclerosis complex-associated seizures in the EXIST-3 study. Recommendations have been made for the target C range of everolimus for therapeutic drug monitoring (TDM) and the doses necessary to achieve this target C .

Methods: A model-based approach was used to predict patients' daily C . Time-normalized C (TN-C ) was calculated as the average predicted C in a time interval. TN-C was used to link exposure to efficacy and safety end points via model-based approaches. A conditional logistic regression stratified by age subgroup was used to estimate the probability of response in relation to exposure. A multiplicative linear regression model was used to estimate the exposure-response relationship for seizure frequency (SF). An extended Cox regression model was used to link exposure to the time to first adverse event.

Results: There was a strong, consistent, and highly significant relationship between everolimus exposure and efficacy, measured by TN-C and SF, regardless of patient's age and concomitant use of cytochrome P450 3A4 (CYP3A4) inhibitors/inducers. Results of an extended Cox regression analyses indicated that twofold increases in TN-C were not associated with statistically significant increases in the risk of stomatitis or infections.

Significance: The recommended TDM is to target everolimus C within a range of 5-7 ng/mL initially and 5-15 ng/mL in the event of an inadequate clinical response, and safety is consistent with previous reports. Starting doses depend on age and the concomitant use of CYP3A4/P-glycoprotein inducers/inhibitors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.14085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033043PMC
June 2018

Retrospective Study of the Characteristics of Anticoagulant-Type Rodenticide Poisoning in Hong Kong.

J Med Toxicol 2018 09 23;14(3):218-228. Epub 2018 Apr 23.

Hospital Authority Toxicology Reference Laboratory, Princess Margaret Hospital, Kowloon, Hong Kong, People's Republic of China.

Introduction: Warfarin- and superwarfarin-type anticoagulants are commonly used as rodenticides. Exposure to these agents, especially superwarfarins with long-acting anticoagulant effect, can cause life-threatening coagulopathy in humans. Most superwarfarin poisoning cases had an obvious history of exposure, though occult cases without exposure history have also been reported. The current study aims to examine anticoagulant-type rodenticide poisoning in Hong Kong and to identify the similarities and differences between patients with known exposure history and those whose exposure is recognized only through laboratory testing.

Methods: The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. This was a retrospective cohort study of all patients with biochemically confirmed anticoagulant-type rodenticide exposure, from 2010 to 2014.

Results: Superwarfarin was the most common group of anticoagulant-type rodenticides identified (87.8%), in which bromadiolone and brodifacoum were the most frequently encountered. Among the 41 cases identified, 31 had an obvious exposure history, and 10 were occult poisoning in which the context of exposure remained unidentified. All occult poisoning patients without exposure history presented with bleeding events. These occult poisoning cases often went unrecognized by frontline clinicians, leading to delayed investigation and initiation of treatment. This group of patients was associated with a longer time to diagnose coagulopathy (p < 0.001) and confirm rodenticide poisoning (p < 0.05), a higher rate of international normalized ratio (INR) rebound after initiation of antidote (p < 0.001), and a longer time needed for normalizing INR (p < 0.05).

Conclusion: Occult superwarfarin poisoning is an important yet under-recognized differential cause of unexplained coagulopathy. A high index of clinical suspicion and availability of specialized toxicological test for superwarfarins play a vital role in diagnosis and early initiation of appropriate management. The underlying cause of such poisoning remains obscure and warrants further study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13181-018-0660-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097974PMC
September 2018

Increased expression of angiogenic cytokines in CD56+ uterine natural killer cells from women with recurrent miscarriage.

Cytokine 2018 10 1;110:272-276. Epub 2018 Feb 1.

Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Shatin, Hong Kong. Electronic address:

Objective: To compare the expression pattern of angiogenic cytokines in CD56+ uNK cells from peri-implantation endometrium in women with a history of recurrent miscarriage and fertile controls.

Methods: 28 women were recruited, from which 18 women were diagnosed as recurrent miscarriage and 10 women were of proven fertility. Endometrial biopsy samples were obtained precisely 7 days after luteinization hormone surge in a natural cycle. The angiogenic profile of isolated CD56+ uNK cells was determined by RayBio human angiogenesis antibody array G Series 1000. Differentially expressed angiogenic cytokines between groups were validated by ELISA kits.

Results: CD56+ uNK cells freshly isolated from peri-implantation endometrium were determined to be >90% pure. Angiogenic cytokine array demonstrated that CD56+ uNK cells are one of the angiogenic factors producers in endometrium around the time of embryo implantation. A differential angiogenic cytokine expression profile was found between two groups, with significantly higher expressions of angiogenin, VEGF-A and bFGF in CD56+ uNK cells from women with recurrent miscarriage, compared with fertile controls.

Conclusions: Differential angiogenic cytokine profile of isolated CD56+ uNK cells suggested the role of uNK cells in the altered endometrial vascularity at the time of implantation, which may account for the endometrial contribution to recurrent miscarriage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2018.01.013DOI Listing
October 2018

Change in death metaphors among university students in Hong Kong from 2004 to 2016.

Death Stud 2019 30;43(1):32-40. Epub 2018 Mar 30.

a Department of Applied Social Sciences , City University of Hong Kong , Hong Kong.

Death metaphors are a meaningful way to understand personal perceptions of death, an important construct affecting how people live. This study collected death metaphor data among 100 university students in Hong Kong in 2016 and compared the findings with another study reported in 2004. Interpersonally oriented death metaphors were still popular among students a decade later. There was a general decrease in positive perception of death and an increase in negative perception of death from 2004 to 2016. Death metaphors are useful tools in death education programs, especially in cultures where death is a taboo topic.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/07481187.2018.1432720DOI Listing
August 2019

Intravenous fluid selection rationales in acute clinical management.

World J Emerg Med 2018 ;9(1):13-19

Accident and Emergency Department, Tuen Mun Hospital, Hong Kong, China.

Background: Intravenous fluid (IVF) is commonly used in acute clinical management. This study aimed to review the choice and primary considerations in IVF prescriptions and to evaluate the adequacy of guidelines and trainings on it in the New Territories West Cluster (NTWC) of Hong Kong.

Methods: This is a descriptive study based on data collected from an online survey. Data were processed by SPSS for statistical analysis. This study focused on a general description and doctor-nurse between group comparison. Participants were asked the choice of IVF for nine acute clinical scenarios and provide reason. A 1-10 scale was used to assess the sufficiency of guideline, training and information, and time for revision on IVF prescription.

Results: 0.9% sodium chloride was the most familiar IVF (36%), followed by 5% Dextrose solution (26%). In the nine scenarios, the most chosen IVF was 0.9% sodium chloride (37%-61%). There was significant difference in the choice of IVF between doctors and nurses in 7 cases. The second most chosen IVF for doctors was Plasma-Lyte A while that for nurses was Gelofusine. Departmental practice was the most chosen reason to account for the prescription. The adequacy of guideline, information and training, and time for revision was rated 5. Doctors had significantly more time at work than nurses to update knowledge in IVF prescription (5.41 versus 4.57).

Conclusion: 0.9% sodium chloride was mostly chosen. The choice of IVF was mainly based on departmental practice. Adequacy of guideline, information and training, and time for revision on IVF prescription were average, indicating significant training deficit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5847/wjem.j.1920-8642.2018.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717370PMC
January 2018

Thymosin β4 for the treatment of acute stroke in aged rats.

Neurosci Lett 2017 10 31;659:7-13. Epub 2017 Aug 31.

Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA; Department of Physics, Oakland University, Rochester, MI 48309, USA. Electronic address:

Thymosin β4 (Tβ4) is a 5K peptide which influences cellular migration by inhibiting organization of the actin-cytoskeleton. Tβ4 has neurorestorative properties and is a potential candidate for the treatment of sub-acute stroke. Previous research demonstrated that Tβ4 improved neurological outcome in a young (3 months) rat model of embolic stroke. We hypothesized that Tβ4 would improve neurological outcome in an aged rat model of embolic stroke when administered 24h after embolic stroke. Aged Male Wistar rats (Charles River, France 18-21 months) were subjected to embolic middle cerebral artery occlusion (MCAo). Rats were randomized to receive Tβ4 (12mg/kg, RegeneRx Biopharmaceuticals, Inc.) or control 24h after MCAo and then every 3days for 4 additional doses. The dose of 12mg/kg was the maximal dose of Tβ4 that showed functional improvement in a young rat model of embolic stroke. Functional tests (adhesive-removal test (ART), foot fault test (FFT) and the modified Neurological Severity Score (mNSS)) were performed weekly. The rats were sacrificed 56days after MCAo and lesion volumes were measured. Immunohistochemical analysis for oligodendrogenesis, myelination and gliosis was also performed. Twenty-three rats were included in the study: control group (n=12) and Tβ4 group (n=11). After randomization, there were three deaths in both the control and Tβ4 groups. The Tβ4 treatment reduced infarct volume by more than 50% (12.8%±9.3%, mean±SE, p<0.05) compared to the control group (26.0%±4.3%). However, Tβ4 did not show improvement in functional outcome compared to control. There was no significant increase in oligodendrogenesis, myelination and gliosis between control and treatment with Tβ4, however, we unexpectedly observed that overall (control and Tβ4 groups) astrocytic gliosis as measured by GFAP immunoreactivity was significantly inversely correlated with neurological outcome measured using the modified Neurological Severity Score (mNSS) (p<0.01), suggesting that greater gliosis may be related to improvement of neurological outcome in aged rats. In summary, Tβ4 treatment of stroke aged rats significantly reduces infarct volume compared to vehicle treated stroke, however, Tβ4 treatment did not show improvement in functional outcome, myelination or gliosis when compared to control. GFAP staining was significantly inversely correlated to improvement in the mNSS, suggesting that gliosis in the aged rat may be of benefit in improvement of functional outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neulet.2017.08.064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624853PMC
October 2017

Indazole-based ligands for estrogen-related receptor α as potential anti-diabetic agents.

Eur J Med Chem 2017 Sep 14;138:830-853. Epub 2017 Jul 14.

Janssen Research & Development, LLC, Welsh and McKean Roads, Spring House, PA 19477-0776, USA. Electronic address:

Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that has been functionally implicated in the regulation of energy homeostasis. Herein is described the development of indazole-based N-alkylthiazolidenediones, which function in biochemical assays as selective inverse agonists against this receptor. Series optimization provided several potent analogues that inhibited the recruitment of a co-activator peptide fragment in vitro (ICs < 50 nM) and reduced fasted circulating insulin and triglyceride levels in a sub-chronic pre-diabetic rat model when administered orally (10 mg/kg). A multi-parametric optimization strategy led to the identification of 50 as an advanced lead, which was more extensively evaluated in additional diabetic models. Chronic oral administration of 50 in two murine models of obesity and insulin resistance improved glucose control and reduced circulating triglycerides with efficacies similar to that of rosiglitazone. Importantly, these effects were attained without the concomitant weight gain that is typically observed with the latter agent. Thus, these studies provide additional support for the development of such molecules for the potential treatment of metabolic diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmech.2017.07.015DOI Listing
September 2017

An animal model of co-existing sarcopenia and osteoporotic fracture in senescence accelerated mouse prone 8 (SAMP8).

Exp Gerontol 2017 10 12;97:1-8. Epub 2017 Jul 12.

Musculoskeletal Research Laboratory, Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong Special Administrative Region; The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, People's Republic of China. Electronic address:

Sarcopenia and osteoporotic fracture are common aging-related musculoskeletal problems. Recent evidences report that osteoporotic fracture patients showed high prevalence of sarcopenia; however, current clinical practice basically does not consider sarcopenia in the treatment or rehabilitation of osteoporotic fracture. There is almost no report studying the relationship of the co-existing of sarcopenia and osteoporotic fracture healing. In this study, we validated aged senescence accelerated mouse prone 8 (SAMP8) and senescence accelerated mouse resistant 1 (SAMR1) as animal models of senile osteoporosis with/without sarcopenia. Bone mineral density (BMD) at the 5th lumbar and muscle testing of the two animal strains were measured to confirm the status of osteoporosis and sarcopenia, respectively. Closed fracture was created on the right femur of 8-month-old animals. Radiographs were taken weekly post-fracture. MicroCT and histology of the fractured femur were performed at week 2, 4 and 6 post-fracture, while mechanical test of both femora at week 4 and 6 post-fracture. Results showed that the callus of SAMR1 was significantly larger at week 2 but smaller at week 6 post-fracture than SAMP8. Mechanical properties were significantly better at week 4 post-fracture in SAMR1 than SAMP8, indicating osteoporotic fracture healing was delayed in sarcopenic SAMP8. This study validated an animal model of co-existing sarcopenia and osteoporotic fracture, where a delayed fracture healing might be resulted in the presence of sarcopenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exger.2017.07.008DOI Listing
October 2017