The effect of subchondral oedema in T2-weighted Dixon MRI sequence evaluation of sacroiliac joint erosion in axial spondyloarthropathy.

AIM: To evaluate the effect of subchondral oedema in T2-weighted Dixon magnetic resonance imaging (MRI) sequence evaluation of sacroiliac joint erosion in patients with axial spondyloarthropathy. MATERIALS AND METHODS: Twenty patients diagnosed with axial spondyloarthritis underwent MRI at a tertiary referral centre from December 2019 to March 2021 were included. In-phase, opposed-phase and fat-only images were scored by two musculoskeletal radiologists independently for the presence of erosions in eight sacroiliac joint quadrants. Sensitivity, specificity and areas under the curve (AUC) of the receiver operating characteristic curve were determined using T1W sequence as reference standard. Intra-observer and interobserver reliability were calculated using Cohen's kappa coefficient. RESULTS: The diagnostic performance of fat-only and in-phase images were similar (AUC 0.857-0.902 and 0.828-0.868) and better than opposed-phase images (AUC 0.613-0.658). The interobserver reliability of fat-only and in-phase images were substantial (k = 0.747 and 0.712), and moderate for opposed-phase images (k = 0.417). Intra-observer reliability was almost perfect for all the images. In the subgroup analysis, the specificity and AUC for oedema-positive group were lower than oedema-negative group in all image sets. Interobserver reliability was substantial for fat-only and in-phase images in both groups, but slight and moderate for the opposed-phase oedema-positive and negative groups, respectively. CONCLUSION: The presence of subchondral oedema in active sacroiliitis decreased the diagnostic accuracy of sacroiliac joint erosion detection on T2W Dixon MRI images.

Sacral tumours and their mimics: pictorial review and diagnostic strategy.

Sacral tumours encompass an extensive range of differential diagnosis. The clinical presentation is often non-specific, including neurological deficits and low back pain. Accurate diagnosis of sacral lesions is challenging and requires a comprehensive imaging strategy and robust knowledge on the imaging characteristics of different pathological processes. This review will provide an updated overview of the computed tomography (CT), magnetic resonance imaging (MRI), and integrated positron-emission tomography (PET)-CT features of some common and rare sacral tumours and their mimics. Several clinical scenarios with specific diagnostic considerations and treatment implications will be described.

Generation and Characterization of Patient-Specific iPSC Model for Cardiovascular Disease.

Advances in differentiation of cardiomyocytes from human induced pluripotent stem cell (hiPSC) were emerged as a tool for modeling of cardiovascular disease that recapitulates the phenotype for the purpose of drug screening, biomarker discovery, and testing of single-nucleotide polymorphism (SNP) as a modifier for disease stratification. Here, we describe the (1) retroviral reprogramming strategies in the generation of human iPSC, (2) methodology in characterization of iPSC in order to identify the stem cell clones with the best quality, and (3) protocol of cardiac differentiation by modulation of Wnt signaling and ß-catenin pathway.

Statins and downstream inhibitors of the isoprenylation pathway increase type 2 iodothyronine deiodinase activity.

The type 2 iodothyronine selenodeiodinase (D2) is a critical determinant of local thyroid signaling, converting T(4) to the active form T(3) at the cytoplasmic face of the endoplasmic reticulum, thus supplying the nucleus with T(3) without immediately affecting circulating thyroid hormone levels. Although inhibitors of the cholesterol synthesis/isoprenylation pathway, such as hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (statins) have been to shown to down-regulate selenoproteins via interruption of normal selenocysteine incorporation, little is known about the effect of statins on D2. Here, we report that statins and prenyl transferase inhibitors actually increase D2 activity in cells with endogenous D2 expression. Although we confirmed that lovastatin (LVS) decreases the activity of transiently expressed D2 in HEK-293 cells, the prenyl transferase inhibitors increase activity in this system as well. LVS treatment increases endogenous Dio2 mRNA in MSTO-211H cells but does not alter transiently expressed Dio2 mRNA in HEK-293 cells. The prenyl transferase inhibitors do not increase Dio2 mRNA in either system, indicating that a posttranscriptional mechanism must exist. Cotreatment with LVS or the prenyl transferase inhibitors with the proteasome inhibitor MG-132 did not lead to additive increases in D2 activity, indirectly implicating the ubiquitin-proteasomal system in the mechanism. Finally, C57BL/6J mice treated with LVS or farnesyl transferase inhibitor-277 for 24 h exhibited increased D2 activity in their brown adipose tissue. These data indicate that statins and downstream inhibitors of the isoprenylation pathway may increase thyroid signaling via stimulation of D2 activity.

The nursing gaze: power relations in a study of nurse-resident interactions in learning disability.

The researchers observed nurse-resident interactions in learning disability units in Hong Kong and interviewed a purposeful sample of nurses who had varying levels of interaction. The median interaction rate between nurses and residents was 27.5% with most interactions relating to physical care. When not interacting with residents, nurses performed administrative tasks. Factors that influenced nurses' interactions revolve around their orientation to a new clinical setting, stresses in the care setting and nurses' coping strategies, contextual constraints, and nurses' prioritization of care. Support for Goffman's self-mortification principle, Foucault's notion of the clinical gaze and infantilism theory were evident in the practice of the nurses studied.

Psychosocial adjustment of people with epilepsy in Hong Kong.

PURPOSE: In light of the issues associated with the psychosocial adjustment of people with epilepsy that have been widely reported, this study examined these issues within a Chinese cultural context. METHODS: Fifty patients with epilepsy completed The Washington Psychosocial Inventory, the Coping Inventory for Stressful Situations, and a questionnaire that assessed their psychosocial difficulties and coping styles. Multiple regression procedure was used to examine the strength of various medical and social factors in predicting the psychosocial adjustment problems of these participants. RESULTS: Social factors, such as self-perception and coping strategies, were more powerful predictors of psychosocial adjustment in people with epilepsy than the medical factors associated with epilepsy. CONCLUSIONS: These findings showed that psychosocial maladjustment is a significant issue for people with epilepsy in Hong Kong. The emerging importance of social factors as predictors of psychosocial adjustment in epilepsy, as compared with medical factors, highlights the need for developing tailored counseling therapy and social support groups for people with epilepsy.

Imbalance between cell proliferation and cellular DNA fragmentation in hepatocellular carcinoma.

AIM/BACKGROUND: Hepatocellular carcinoma (HCC) is known for its rapid growth. This study was undertaken to determine the expression of proliferative markers, apoptosis (DNA fragmentation) and oncogene products known to regulate apoptosis (p53, bcl-2) in HCC. METHODS: 150 Chinese patients with HCC were studied (M:F 128:22, age 14-88 years). Immunohistochemistry was employed to detect cell proliferative markers (PCNA, Ki67), and oncogene products known to regulate apoptosis (p53, bcl-2). DNA fragmentation was determined by terminal dUTP nick end labeling (TUNEL). RESULTS: 98% and 95% of HCC had PCNA (median 2+) and Ki67 (median 2+) detected respectively. TUNEL labeling was detected in only a small number of tumor cells (no labeling in 11%, median 1/1000 cell labeled, range: 0-70/1000 cells). There was no correlation between TUNEL labeling and the clinical parameters (sex, age, cirrhosis, and survival) and the expression of cell proliferative markers. p53 was detected in 53% of the patients (median 1+, range: 0-4+) and bcl-2 was detected in a small proportion of tumor cells in only 13% of the HCCs (range: 0-1 +). The expression of p53 and Bcl-2 did not correlate with TUNEL labeling or the natural survival. CONCLUSIONS: Cell proliferation in HCC is unmatched by apoptosis, accounting for the rapid growth of this tumor. This lack of apoptosis in HCC is unrelated to the expression of p53 or bcl-2 over-expression.

Immobilized yeast bioreactor systems for continuous beer fermentation

Two different types of immobilized yeast bioreactors were examined for continuous fermentation of high-gravity worts. One of these is a fluidized bed reactor (FBR) that employs porous glass beads for yeast immobilization. The second system is a loop reactor containing a porous silicon carbide cartridge (SCCR) for immobilizing the yeast cells. Although there was some residual fermentable sugar in the SCCR system product, nearly complete attenuation of the wort sugars was achieved in either of the systems when operated as a two-stage process. Fermentation could be completed in these systems in only half the time required for a conventional batch process. Both the systems showed similar kinetics of extract consumption, and therefore similar volumetric productivity. As compared to the batch fermentation, total fusel alcohols were lower; total esters, while variable, were generally higher. The yeast biomass production was similar to that in a conventional fermentation process. As would be expected in an accelerated fermentation system, the levels of vicinal diketones (VDKs) were higher. To remove the VDKs, the young beer was heat-treated to convert the VDK precursors and processed through a packed bed immobilized yeast bioreactor for VDK assimilation. The finished product from the FBR system was found to be quite acceptable from a flavor perspective, albeit different from the product from a conventional batch process. Significantly shortened fermentation times demonstrate the feasibility of this technology for beer production.

Histological changes of concurrent hepatitis C virus infection in asymptomatic hepatitis B virus patients.

In chimpanzees and in vitro cell culture studies, hepatitis C infection has been shown to suppress hepatitis B virus expression. In addition, hepatitis C infection can cause much more severe liver disease in patients chronically infected with hepatitis B virus. The aims of the present study were to determine the prevalence of hepatitis C infection in asymptomatic chronic hepatitis B Hong Kong Chinese patients and the histological changes and hepatic expression of hepatitis B virus and hepatitis C virus. Five hundred and seventy-one Hong Kong Chinese asymptomatic chronic hepatitis B patients were studied. Only four (0.7%) were hepatitis C virus antibody positive; they were also all positive for hepatitis C viral RNA in serum by reverse transcription-polymerase chain reaction (RT-PCR). Portal lymphoid aggregates and bile duct damage was noted in the liver sections of three of the four patients. Hepatic expression of hepatitis B surface antigen was detected in three patients; none had detectable hepatitis B core antigen. By branched DNA assay, serum hepatitis B DNA could not be detected in any of the four patients, but three had hepatitis C RNA. By in situ RT-PCR, hepatitis C RNA was detected in the cytoplasm of three of the four patients. These findings suggest that hepatitis C coinfection in asymptomatic chronic hepatitis B patients is uncommon in Hong Kong Chinese and active hepatitis B viral replication is absent in these patients.

The reduction in alcohol intake in rats by isoproterenol is attenuated by indomethacin but not enalapril: relationship to blood glucose levels.

Many adrenergic agonists including isoproterenol, a beta1,2-adrenergic agonist, reduce alcohol consumption, but the mechanism of this effect is not known. Adrenergic agonists have a variety of effects, among which are their ability to raise both angiotensin (ANG) II activity and plasma glucose levels. Previous research has shown that ANG II and enhanced glucose levels are accompanied by reductions in alcohol intake. Therefore, the following experiments assessed the roles of each of these factors in the suppression of alcohol intake by isoproterenol. Male Wistar rats were trained to drink a quantity of 6% (w/v) alcohol using the limited access procedure, which offers a daily 40-min access to alcohol and water. In experiment 1, isoproterenol or vehicle was administered s.c. just prior to alcohol availability, and only the group receiving isoproterenol showed a marked reduction in alcohol intake. Following this, the groups were pretreated i.p. with either vehicle or ascending doses of the prostaglandin synthetase inhibitor, indomethacin (2, 4 mg/kg), followed by either isoproterenol or vehicle. Control groups received either two vehicle injections or vehicle and indomethacin. Indomethacin alone did not affect alcohol intake at any of the doses tested but did dose-dependently attenuate the reduction in alcohol intake produced by isoproterenol. In experiment 2, isoproterenol was administered just prior to alcohol availability and when the suppression of alcohol intake stabilized, ascending doses of the angiotensin converting enzyme inhibitor, enalapril (1, 20, 40 mg/kg), were given i.p. 1 h prior to the isoproterenol. Enalapril altered water intake but had no effect on the isoproterenol-induced reduction in alcohol intake. These results show that the inhibition of alcohol drinking by isoproterenol varies more closely with altered glucose levels than with increased ANG II synthesis. They also demonstrate that downstream consequences of a drug may play a role in its effect on alcohol intake.

The reduction in alcohol intake by the 5-HT1A agonist 8-OH DPAT and its attenuation by the alpha 2 adrenergic antagonist idazoxan correlates with blood glucose levels.

Serotonergic agents in general and the 5-HT1A agonist 8-OH DPAT in particular, reduce alcohol intake in rats and primates but the mechanism of this effect is not known. Previous studies have shown a correlation between alcohol consumption and the propensity to consume sweet substances. Indeed, certain biochemical events accompanying glucose utilization have been proposed as satiety signals in the control of feeding. Since 8-OH DPAT produces hyperglycemia, we tested the hypothesis that its effect on alcohol intake may be partly mediated through an increase blood glucose. Male Wistar rats were trained to drink a bout of 6% (w/v) alcohol using the limited access procedure which offers a daily 40-min access to alcohol and water. On consecutive test trial days separated by intervening non-drug days, the amount of alcohol consumed (1 g/kg on intervening days) was measured following the administration of 8-OH DPAT (150 micrograms/kg 10 min prior to drinking) alone or in combination with the prior (20 min) injection of idazoxan (2 mg/kg), an alpha-2 adrenoceptor antagonist with hypoglycemic properties. Idazoxan attenuated the hyperglycemic effect of 8-OH DPAT and completely reversed 8-OH DPAT's inhibitory effect on alcohol intake. Idazoxan alone produced a mild hypoglycemia and stimulated alcohol intake. These results support a role for glucoregulatory processes in serotonergically-mediated changes in alcohol consumption.

Attributes of nurses that determine the quality of care for mentally handicapped people in an institution.

This is an ethnographic study that examines, from the relatives' perspective, the attributes of nurses that are considered important in the caring process of mentally handicapped people in an institutional setting in Hong Kong. Twelve interviews were carried out with a family member who had a relative living in a special unit for severely mentally handicapped people. Empirical studies, mainly from the west, have shown that decisions to place a mentally handicapped family member in residential care is a complex process. Family characteristics, the relatives' characteristics as well as the availability of support, have been found to influence decisions about out-of-home placement. Once this decision has been made, a new caring relationship between nurse, family and relative needs to be established. The final categories that emerged from the data show that families have expectations about the nurses' competence and commitment to the job and about their relationships with the client and the family. Consequently quality is judged, not only by the way in which nurses work with the clients, but also by the way in which they work with the family. Implications for practice and education of nurses working with mentally handicapped people and for nursing administration in Hong Kong are discussed.

Classification of hepatocellular carcinoma according to hepatocellular and biliary differentiation markers. Clinical and biological implications.

Hepatocellular carcinoma (HCC) is a heterogeneous disease. HCC derived from different stages of cellular differentiation may have different clinical and pathobiological behavior. To test the hypothesis that HCC can be classified into two types based on its phenotypic markers (hepatocellular and biliary differentiation), liver tissues from 290 Chinese patients with HCC were studied. Expression of hepatocytic differentiation marker (HEP-PAR-reactive antigen), biliary differentiation markers (AE1-AE3, cytokeratin-19), proliferation markers (Ki-67, proliferating cell nuclear antigen), alpha-fetoprotein, p53, and transforming growth factor-alpha in the tumor tissue were assessed by immunohistochemistry. Hepatocytic differentiation marker was detected in 99.7% and biliary differentiation markers were detected in 29.3% of these tumors. Clinically, no patient with HCC with biliary markers survived for more than 27 weeks compared with a 22.6% survival rate in patients with HCC negative for biliary markers. HCCs positive for the biliary differentiation markers showed features of more aggressive disease in terms of poorer cellular differentiation (P < 0.001) and high-level expression of proliferation markers (Ki-67, P < 0.001; proliferating cell nuclear antigen, P = 0.0114) compared with HCCs without biliary markers. HCCs with biliary markers also had a higher level of expression of alpha-fetoprotein (P < 0.001) and p53 (P = 0.0077). Classification of HCCs based on its phenotypic (differentiation) markers has both clinical and pathobiological implications.

Recent developments on the hazards posed by 2,3,7,8-tetrachlorodibenzo-p-dioxin in soil: implications for setting risk-based cleanup levels at residential and industrial sites.

Since the publication of the Times Beach risk assessment in 1984, which suggested that residential soils were of concern when the level of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was in excess of 1 ppb, there has been continued interest in this topic. Studies conducted within the past 5 yr on the environmental and toxicological behavior of TCDD, as well as refinement of parameters regarding human exposure, indicate that previous assessments of the risk to humans posed by TCDD-contaminated soil were overestimated. In this paper, recent information drawn from nearly 100 recently published articles regarding the histopathology interpretation of the Kociba bioassay, environmental fate and half-life of TCDD in soil, and estimates of human exposure via soil ingestion, dermal contact, inhalation, surface runoff, and the consumption of fish were incorporated into a risk assessment. Cleanup levels for TCDD in residential and industrial soils were calculated based on most likely exposure scenarios. Probability distributions of key exposure parameters were incorporated into a Monte Carlo uncertainty analysis to predict the range and probability of TCDD uptake and corresponding cleanup levels in soil. This analysis demonstrated that the most significant route of human exposure to TCDD is through dermal contact with soil, followed by soil ingestion, fish consumption, and inhalation of airborne particulates. At residential sites, soils containing 20 parts per billion (ppb) of TCDD were found to pose a lifetime cancer risk no greater than 1 in 100,000 (10(-5) risk) under typical exposure conditions. Based on the Monte Carlo analysis, soil concentrations for the 75th and 95th percentile person were 12 and 7 ppb (10(-5) risk), respectively. In industrial soils, TCDD concentrations ranged between 131 and 582 ppb (10(-5) risk), depending on the amount of time spent outdoors under typical exposure conditions. Industrial soil concentrations of approximately 93 and 46 ppb (10(-5) risk) were calculated for the 75th and 95th percentile worker, respectively, engaged in outdoor activities. The range of TCDD concentrations in industrial soils was not reduced significantly when the consumption of fish from a neighboring waterway by off-site receptors was considered. While cleanup levels for TCDD should be derived on a site-specific basis, this analysis indicated that soil cleanup standards can be generally higher than those implemented over the past 8 yr.

The potential inhalation hazard posed by dioxin contaminated soil.

Mathematical models and field data were used to estimate the airborne concentrations of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) vapor and particulates which could originate from soil containing 100 ppb TCDD. The model of Jury et al. (1983) and the box approach were used to predict the concentration of TCDD vapor from soil. The daily soil temperature was assumed to vary between 20 degrees C and 40 degrees C for six months of the year to account for diurnal warming and cooling of the soil. The depth of contamination was 50 mm. The model predicted average vapor flux rate for TCDD from soil for this temperature profile was 1.5 x 10(-14) mg/sec-cm2. The upper-bound estimates of the TCDD vapor concentration on-site at 40 degrees C and 20 degrees C were 2.5 pg/m3 and 1.8 pg/m3, respectively. Using a recently proposed unit risk value (URV) of 2.9 x 10(-6) (pg/m3)-1 [slope factor = 1.0 x 10(-14) (mg/kg-day)-1], the maximum plausible cancer risk is about 1 x 10(-5). If one accepts the EPA URV of 3.3 x 10(-5) (pg/m3)-1 (slope factor = 1.2 x 10(-13) (mg/kg-day)-1), then the risk is no greater than 1 x 10(4). A maximum TCDD vapor concentration of 0.21 pg/m3 was predicted 100 meters downwind (for summer days). The on-site concentration of TCDD in suspended particulate was estimated to be 1.4 pg/m3 (based on a TSP level of 0.07 mg/m3 from site soil). For persons exposed to vapors and particulates about 100 meters off-site, the exposure was about 10-fold less.(ABSTRACT TRUNCATED AT 250 WORDS)

An assessment and quantitative uncertainty analysis of the health risks to workers exposed to chromium contaminated soils.

Millions of tons of chromite-ore processing residue have been used as fill in various locations in Northern New Jersey and elsewhere in the United States. The primary toxicants in the residue are trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)]. The hazard posed by Cr(III) is negligible due to its low acute and chronic toxicity. In contrast, Cr(VI) is considered a inhalation human carcinogen at high concentrations. Approximately 40 commercial and industrial properties in Northern New Jersey have been identified as containing chromite ore processing residue in the soil. One site, a partially-paved trucking terminal, was evaluated in this assessment. The arithmetic mean and geometric mean concentrations of total chromium in soil were 977 and 359 mg/kg, respectively. The data were log-normal distributed. The arithmetic mean and geometric mean concentrations of Cr(VI) in surface soil were 37.6 and 3.1 mg/kg, respectively. The data could not be fit to a standard distribution, likely due to the large number of samples with concentrations below the method detection limit (65%). Dose was calculated for each exposure route using a Monte Carlo statistical simulation. Probability distributions of most exposure parameters were incorporated into the analyses to predict the range and probability of uptake for persons in the exposed population. The exposure parameter distributions included in this assessment are: the concentrations of Cr(VI) and total chromium in air and soil, fraction of the year when suspension of airborne soil particulates is likely to occur due to weather conditions, fraction of Cr(VI) in air which is respirable (less than 10 microns), soil loading rate on skin, occupational tenure, and body weight. The techniques used in this assessment are applicable for evaluating the human health risks posed by most industrial sites having contaminated soil. The estimated average daily dose (ADD) via ingestion and dermal absorption for the individual exposed at the 95th percentile was about 48,000- and 91-fold below the U.S. EPA reference dose (RfD) for Cr(III) and Cr(VI), respectively. Since inhalation of Cr(VI) contaminated dust (but not ingestion or dermal contact) poses a cancer hazard, the lifetime average daily doses (LADDs) associated with exposure at the 50th and 95th percentile were calculated to be 9.8 x 10(-8) and 1.3 x 10(-6), respectively. Based on this analysis, industrial sites having soil concentrations of Cr(VI) below 230 ppm do not pose a significant noncarcinogenic or carcinogenic health hazard following acute or chronic exposure. These risks would be even smaller if the sites were paved.