Uveal and conjunctival melanomas: disease course and outcomes in Chinese patients.

INTRODUCTION: Epidemiological studies of ocular melanomas have largely focused on Caucasian populations. This study reviewed the course and outcomes of uveal melanoma (UM) and conjunctival melanoma (CM) in Chinese patients. METHODS: This retrospective study included patients with UM and CM who received treatment in a tertiary eye centre in Hong Kong from January 1994 to December 2019. Data were recorded concerning patient demographics, tumour laterality, tumour characteristics, investigations performed, treatment regimen, and final outcomes. RESULTS: During the 25-year study period, there were 13 patients with UM and 11 patients with CM who did not display nodal or systemic involvement at diagnosis. The mean ± standard deviation ages at diagnosis of UM and CM were 59 ± 15.8 and 57 ± 13.9 years, respectively. There were more men among patients with UM than among those with CM (P=0.042). Most patients with UM underwent primary enucleation (n=12; 92.3%), whereas most patients with CM underwent orbital exenteration (n=9; 81.8%). The prognosis was significantly worse for CM than for UM. The median disease-free survival were 5.2 years (range, 0.7-20.5) and 2.1 years (range, 0.1-24.9) for UM and CM, respectively. Melanoma-related mortality was significantly higher among patients with CM than among those with UM (P=0.006). CONCLUSION: Compared with UM, CM has higher rates of systemic metastasis and tumour-related mortality in Hong Kong Chinese patients, regardless of prior definitive treatment.

Ocular Sebaceous Carcinoma In Situ With Biphenotypic Differentiation: A Reappraisal of the Alternative Origin of the Tumor.

Ocular sebaceous carcinoma is an uncommon, aggressive tumor arising from the Meibomian gland, Zeis gland, or sebaceous glands in the caruncle or eyelashes. We described a rare case of sebaceous carcinoma in situ in a 51-year-old female that was characterized by intraepithelial growth of sebaceous carcinoma cells with no invasive carcinoma in the underlying sebaceous glands. Early stromal invasion was identified that featured 2 distinctive but focally intermixed populations of sebaceous carcinoma cells and squamous carcinoma cells. The 2 populations of cells exhibited their respective distinct immunophenotype but both showed strong overexpression of p53. This case provides evidence to support the hypothesis that some ocular sebaceous carcinoma may arise from intraepithelial pluripotent stem cells.

Comparing mask fit and usability of traditional and nanofibre N95 filtering facepiece respirators before and after nursing procedures.

BACKGROUND: The reliability of N95 filtering facepiece respirators (FFRs) depends on correct fitting. The perceived usability of FFRs is equally important because discomfort during usage may affect compliance. Body movements during nursing procedures may also increase the risk of face seal leakage. AIM: To evaluate the mask fit and usability of the best-fitting 3M N95 FFR and the nanofibre N95 FFR before and after nursing procedures. The physical properties of these FFRs were also examined. METHODS: This experimental study had a one-group multiple comparison design. In total, 104 nursing students participated, and performed nursing procedures for 10 min when wearing the best-fitting 3M FFR and the nanofibre FFR. Mask fit and perceived usability of the FFRs were evaluated. FINDINGS: More participants failed to obtain a fit factor ≥100 when using the best-fitting 3M FFR than when wearing the nanofibre FFR (33.7% vs 21.2%) after the procedures (P=0.417). The nanofibre FFR also demonstrated higher usability than the 3M FFRs in terms of facial heat, breathability, facial pressure, speech intelligibility, itchiness, difficulty of maintaining the mask in place, and comfort level (P<0.001). The nanofibre FFR was also lighter, thinner and had slightly higher bacterial filtration efficiency than the 3M FFRs. CONCLUSION: The nanofibre FFR demonstrated significantly better usability than the 3M FFRs. None of the respirators were able to provide consistent protection for the wearer, as detected by face seal leakage after performing nursing procedures. Further improvement in the prototype design is needed to increase compliance and ensure the respiratory protection of users.

Comparison of antioxidant activities of different parts from snow chrysanthemum (Coreopsis tinctoria Nutt.) and identification of their natural antioxidants using high performance liquid chromatography coupled with diode array detection and mass spectrometry and 2,2'-azinobis(3-ethylbenzthiazoline-sulfonic acid)diammonium salt-based assay.

Snow chrysanthemum (Coreopsis tinctoria Nutt.), a world-widely well-known flower tea material, has attracted more and more attention because of its beneficial health effects such as antioxidant activity and special flavor. In this study, a high performance liquid chromatography coupled with diode array detection and mass spectrometry (HPLC-DAD-MS) and 2,2'-azinobis(3-ethylbenzthiazoline-sulfonic acid)diammonium salt (ABTS) based assay was employed for comparison and identification of antioxidants in different samples of snow chrysanthemum. The results showed that snow chrysanthemum flowers possessed the highest while stems presented the lowest antioxidant capacities. Fourteen detected peaks with antioxidant activity were temporarily identified as 3,4',5,6,7-pentahydroxyflavanone-O-hexoside, chlorogenic acid, 2R-3',4',8-trihydroxyflavanone-7-O-glucoside, flavanomarein, flavanocorepsin, flavanokanin, quercetagitin-7-O-glucoside, 3',5,5',7-tetrahydroxyflavanone-O-hexoside, marein, maritimein, 1,3-dicaffeoylquinic acid, coreopsin, okanin and acetyl-marein by comparing their UV spectra, retention times and MS data with standards or literature data. Antioxidants existed in snow chrysanthemum are quite different from those reported in Chrysanthemum morifolium, a well-known traditional beverage in China, which indicated that snow chrysanthemum may be a promising herbal tea material with obvious antioxidant activity.

Reference ranges for lymphocyte subsets among healthy Hong Kong Chinese adults by single-platform flow cytometry.

Race, age, sex, and environmental conditions have significant impacts on lymphocyte subset values. It is important to establish the local reference ranges from healthy and non-HIV-positive adults in the local population for clinical decision making. In this study, the reference ranges for lymphocyte subsets among Chinese adults were established by analysis by single-platform flow cytometry of the lymphocyte compositions of 273 healthy adult blood donors between 17 and 59 years of age. The 95% reference ranges for CD3(+) T cells, CD3(+) CD4(+) T helper cells, and CD3(+) CD8(+) T suppressor cells are 723 to 2,271 cells/µl, 396 to 1,309 cells/µl, and 224 to 1,014 cells/µl, respectively. The 95% reference ranges for CD19(+) B cells and CD56(+) NK cells are 118 to 645 cells/µl and 61 to 607 cells/µl, respectively. Significant gender and age differences in the lymphocyte subsets have been demonstrated. Our results have also shown that the T-lymphocyte compositions in Hong Kong Chinese were comparable to those of other Asian populations but were different from those of Caucasians.

Sensitivity and specificity of the user-seal-check in determining the fit of N95 respirators.

N95 respirators are recommended by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) to prevent the inhalation of droplets which may transmit respiratory pathogens. The reliability of N95 respirators in preventing transmission depends on their fit to the wearer. Quantitative fit testing (QNFT) is the gold standard used to determine this fit objectively. The manufacturers of the respirators also recommend performing a self-reported user-seal-check to detect for leakage. This study aims to investigate the capability of the user-seal-check in determining the fit of N95 respirators by investigating the sensitivity and specificity of the user-seal-check compared with QNFT. A prospective and cross-sectional research design was used. A total of 204 local Chinese undergraduate nursing students were recruited to test two commonly used respirator models (3M 1860S and 3M 1862). The results of the user-seal-check were compared with the results of the gold standard QNFT using the Condensation Nucleus Counter Fit Tester System. The sensitivity and specificity of the user-seal-check results obtained with the respirators were calculated. The results indicated low sensitivity, accuracy and predictive value of the user-seal-check in determining the fit of the N95 respirators. The user-seal-check was not found to be reliable as a substitute for QNFT. The results also suggested that the user-seal-check may be unreliable for detecting gross leakage. We recommend that QNFT is used to determine the fit of N95 respirators.

Depressive symptoms among community-dwelling, post-stroke elders in Hong Kong.

BACKGROUND: Depressive symptoms adversely affect functional recovery among post-stroke elders. Such symptoms manifest when elders face difficulties in realistic daily living after being discharged. AIMS: The aim of this study was to examine (1) the prevalence of depressive symptoms among community-dwelling post-stroke elders, (2) the relationship between depressive symptoms and demographic and clinical characteristics among community-dwelling post-stroke elders, and (3) the demographic and clinical factors that differentiate post-stroke elders with and without depressive symptoms. METHODS: A descriptive cross-sectional survey was performed on 50 post-stroke elders from a geriatric day clinic. FINDINGS: Depressive symptoms were highly prevalent (68%) among the community-dwelling post-stroke elders. Depressive symptoms were negatively correlated with social support network, social support satisfaction and functional independence. Lastly, poor social support satisfaction and lower functional independence was found to differentiate those post-stroke elders with and without depressive symptoms. CONCLUSION: The inclusion of psychosocial assessment and delivery of appropriate psychosocial interventions to post-stroke elders are recommended.

Isochromosome 7q in Down syndrome.

Isochromosome 7q is not an uncommon chromosomal abnormality. It has been reported in association with Shwachman-Diamond syndrome, Wilms tumor, and hepatosplenic T-cell lymphoma. In other hematolymphoid malignancies, it occurs almost invariably as a secondary change. A notable example is its association with t(4;11)(q21;q23) in acute lymphoblastic leukemia. It has rarely been described in myelodysplastic syndrome and acute myeloid leukemia. We report the occurrence of i(7q) as the primary abnormality in a 2-year-old boy with Down syndrome and minimally differentiated acute myeloid leukemia.

Effect of cellular and receptor activation on the extent of integrin alphaIIbbeta3 internalization.

Previous studies by our laboratory demonstrated that internalization of fibrinogen-bound alphaIIbbeta3 correlated with both a loss of aggregation and a loss of bound fibrinogen from the platelet surface. However, these studies do not address whether cellular activation, receptor activation and/or receptor occupancy are responsible for the observed internalization of alphaIIbbeta3. The present studies were designed to evaluate the roles of cellular and receptor activation states on the alphaIIbbeta3 internalization process. In these studies, washed platelets were allowed to bind FITC-D57, an antialphaIIb monoclonal antibody, and were subsequently treated with ADP, thrombin receptor activation peptide (TRAP) or antiLIBS6 monoclonal antibody. Following flow cytometric analyses for log green fluorescence, rabbit antifluorescein was added, and the samples were re-analyzed for residual/unquenched fluorescence. Because access of the quenching antibody is limited to extracellular/surface-associated fluorescein, protection from quenching by antifluorescein is taken as evidence of internalization. Stimulation of platelets with ADP or TRAP resulted in a significant increase in the percent internalization of alphaIIbbeta3 compared to control (8.7% and 12.8% vs. 2.9%). Addition of cytochalasin E prior to stimulation resulted in a greater than 90% inhibition of both TRAP and ADP-induced internalization, suggesting that activation-dependent internalization is mediated by the actin cytoskeleton. To investigate whether receptor activation increases the extent of alphaIIbbeta3 internalization, platelets were treated with anti-LIBS6, which directly activates alphaIIbbeta3. Stimulation with anti-LIBS6 caused an approximate 8-fold increase in the extent of alphaIIbbeta3 internalization. To evaluate whether the activated pool of alphaIIbbeta3 is preferentially internalized, platelets were incubated with PAC-1, an antibody specific for activated alphaIIbbeta3. Platelets stimulated with TRAP, demonstrated a dose-dependent internalization of PAC-1. However, approximately 29% of total PAC-1 binding was internalized, irrespective of TRAP concentration, suggesting that a constant proportion of activated alphaIIbbeta3 is selectively internalized in platelets. Collectively, these data suggest that alphaIIbbeta3 is internalized to a greater extent in activated platelets in a cytoskeleton-dependent manner. Furthermore, the active conformer of alphaIIbbeta3 is preferentially internalized which may act as a mechanism for downregulating adhesiveness of activated platelets in the circulation.

Proposal for a unified CCN nomenclature.

A proposal is put forth to unify the nomenclature of the CCN family of secreted, cysteine rich regulatory proteins. In the order of their description in the literature, CCN1 (CYR61), CCN2 (CTGF), CCN3 (NOV), CCN4 (WISP-1), CCN5 (WISP-2), and CCN6 (WISP-3) constitute a family of matricellular proteins that regulate cell adhesion, migration, proliferation, survival, and differentiation, at least in part through integrin mediated mechanisms. This proposal is endorsed by the International CCN Society and will serve to eliminate confusion from the multiple names that have been given to these molecules.

Synchronous laparoscopic-assisted right hemicolectomy and right adrenalectomy.

In recent years, minimally invasive surgery has been increasingly employed for the treatment of colorectal and adrenal tumors. We report an 82-year-old woman with synchronous right-sided colonic tumor and right adrenal tumor requiring resection. Preoperative workup showed a 6-cm primary right adrenal tumor with no evidence of invasion to adjacent structures. Laparoscopic removal of the two tumors was achieved with the use of a hand-port device, which assured safe retraction of the liver and meticulous dissection of the adrenal tumor, as well as port site protection during retrieval of the specimens. The whole operation lasted 270 min and our patient made an uneventful recovery.

Feasibility case-controlled study of day-case haemorrhoidectomy.

INTRODUCTION: Haemorrhoidectomy is traditionally an inpatient procedure. With many benefits, the day-surgery arrangement is an attractive alternative. The feasibility of day-surgery haemorrhoidectomy was explored and the hospital days were calculated in a case controlled design. METHODS: A single surgeon's experience of day-surgery haemorrhoidectomy between 1 July 1999 and 31 March 2000 was compared with inpatient haemorrhoidectomy during the same period. The operations were performed at United Christian Hospital Department of Surgery, Hong Kong (a government-funded public hospital). Statistical tests were applied where appropriate. RESULTS: There were 30 day-surgery and 15 inpatient haemorrhoidectomies. The groups were comparable in terms of age, gender, severity of haemorrhoids, method and duration of haemorrhoidectomy, blood loss, residual haemorrhoids, duration of follow up and unplanned readmission rate. Significantly more day-patients received general than spinal anaesthesia. Twenty-six of 30 (87%) patients were successfully discharged after day surgery. Two were admitted for transient fever (< 24 h), one for micturition syncope and one for acute urinary retention. There were four unplanned readmissions after day surgery: one for pain and three for secondary bleeding. All stopped spontaneously. All three unplanned readmissions after inpatient surgery were for secondary bleeding. All stopped spontaneously. Patient stay was significantly shorter for day surgery (1 +/- 1 day) than for the inpatient arrangement (4 +/- 1.6 days). CONCLUSION: Day-surgery haemorrhoidectomy is feasible. The significantly shorter hospital stay implies savings in public medical expenses.

Localization of an integrin binding site to the C terminus of talin.

Talin, consisting of a 47-kDa N-terminal head domain (residues 1-433) and a 190-kDa C-terminal rod domain (residues 434-2541), links integrins to the actin cytoskeleton. We previously reported that the binding stoichiometry of integrin alpha(IIb)beta(3):talin is approximately 2:1. More recently, an integrin binding site has been localized to the talin head domain. In the present study, we identified another integrin binding site at the C-terminal region of the talin rod domain. In a solid phase binding assay, RGD affinity-purified alpha(IIb)beta(3) bound in a dose-dependent manner to microtiter wells coated with the isolated 190-kDa proteolytic fragment of the talin rod domain. Additionally, alpha(IIb)beta(3) also bound to the talin rod domain captured by 8d4, an anti-talin monoclonal antibody. Polyclonal antibodies raised against a recombinant protein fragment corresponding to the entire talin rod domain (anti-talin-R) inhibited alpha(IIb)beta(3) binding to intact talin by approximately 50% but completely blocked alpha(IIb)beta(3) binding to the talin rod domain. To localize the integrin binding site, we examined alpha(IIb)beta(3) binding to recombinant polypeptide fragments corresponding to partial sequences of the talin rod domain. Whereas alpha(IIb)beta(3) bound effectively to talin-(1075-2541) and talin-(1984-2541), it failed to bind to talin-(434-1076) and talin-(434-1975). Furthermore, the binding of alpha(IIb)beta(3) to talin-(1984-2541) was inhibited by anti-talin-R. These results indicate that an integrin binding site is located within residues 1984-2541 of the talin rod domain. Thus, talin contains two integrin binding sites, one in the homologous FERM (band four-point-one, ezrin, radixin, moesin) domain and another near its C terminus. Because talin exists as an anti-parallel homodimer in focal adhesions, the two integrin binding sites in the adjacent talin molecules would be in close proximity with each other.

The fibrinogen gamma chain dodecapeptide inhibits agonist-induced aggregation of rabbit platelets and fibrinogen binding to rabbit glycoprotein IIb-IIIa.

The HHLGGAKQAGDV (H12) sequence at the carboxyl termini of the y chains and the RGD sequences in the Aalpha chains of human fibrinogen are potential recognition sites for the binding of soluble fibrinogen to glycoprotein IIb-IIIa (GPIIb-IIIa) on activated human platelets. Thus, addition of either H12 or RGD-containing peptides inhibits aggregation of and fibrinogen binding to human platelets. In contrast, we reported previously that RGDS had relatively little inhibitory effect on these functions of rabbit platelets. In the present study, we found that H12 inhibited ADP- and thrombin-induced aggregation of rabbit platelets in a dose-dependent manner. Specificity was demonstrated by the failure of the variant HHLGGAKQAGEV peptide to inhibit ADP-induced aggregation. Furthermore, flow cytometric analyses demonstrated that H12 inhibited the binding of FITC-fibrinogen to ADP-activated rabbit platelets in a dose-dependent manner. To examine the direct interaction of H12 with rabbit GPIIb-IIIa, we performed affinity chromatography by applying an octylglucoside extract of rabbit platelet proteins onto an affinity matrix containing the fibrinogen gamma chain sequence. Proteins of approximately 135 kDa and approximately 95 kDa were specifically eluted by soluble H12, and the 95 kDa protein band was immunoblotted by anti-LIBS1, a monoclonal antibody against human GPIIIa. In control samples, no detectable protein from rabbit platelet lysates was eluted from an RGD affinity matrix by GRGDSP. Collectively, our results demonstrated that H12 inhibits aggregation of and fibrinogen binding to rabbit platelets by directly interacting with rabbit GPIIb-IIIa. These findings suggest that rabbit platelets would serve as a suitable thrombosis model for testing the efficacy of peptide mimetics derived from H12.

Identification of a talin-binding site in the integrin beta(3) subunit distinct from the NPLY regulatory motif of post-ligand binding functions. The talin n-terminal head domain interacts with the membrane-proximal region of the beta(3) cytoplasmic tail.

Following platelet aggregation, integrin alpha(IIb)beta(3) becomes associated with the platelet cytoskeleton. The conserved NPLY sequence represents a potential beta-turn motif in the beta(3) cytoplasmic tail and has been suggested to mediate the interaction of beta(3) integrins with talin. In the present study, we performed a double mutation (N744Q/P745A) in the integrin beta(3) subunit to test the functional significance of this beta-turn motif. Chinese hamster ovary cells were co-transfected with cDNA constructs encoding mutant beta(3) and wild type alpha(IIb). Cells expressing either wild type (A5) or mutant (D4) alpha(IIb)beta(3) adhered to fibrinogen; however, as opposed to control A5 cells, adherent D4 cells failed to spread, form focal adhesions, or initiate protein tyrosine phosphorylation. To investigate the role of the NPLY motif in talin binding, we examined the ability of the mutant alpha(IIb)beta(3) to interact with talin in a solid phase binding assay. Both wild type and mutant alpha(IIb)beta(3), purified by RGD affinity chromatography, bound to a similar extent to immobilized talin. Additionally, purified talin failed to interact with peptides containing the AKWDTANNPLYK sequence indicating that the talin binding domain in the integrin beta(3) subunit does not reside in the NPLY motif. In contrast, specific binding of talin to peptides containing the membrane-proximal HDRKEFAKFEEERARAK sequence of the beta(3) cytoplasmic tail was observed, and this interaction was blocked by a recombinant protein fragment corresponding to the 47-kDa N-terminal head domain of talin (rTalin-N). In addition, RGD affinity purified platelet alpha(IIb)beta(3) bound dose-dependently to immobilized rTalin-N, indicating that an integrin-binding site is present in the talin N-terminal head domain. Collectively, these studies demonstrate that the NPLY beta-turn motif regulates post-ligand binding functions of alpha(IIb)beta(3) in a manner independent of talin interaction. Moreover, talin was shown to bind through its N-terminal head domain to the membrane-proximal sequence of the beta(3) cytoplasmic tail.