Health-related behaviours and mental health in Hong Kong employees.

BACKGROUND: Poor physical and mental health in employees can result in a serious loss of productivity. Early detection and management of unhealthy behaviours and mental health symptoms can prevent productivity loss and foster healthy workplaces. AIMS: To examine health-related behaviours, mental health status and help-seeking patterns in employees, across different industries in Hong Kong. METHODS: Participants were telephone-interviewed and assessed using the Case-finding and Help Assessment Tool (CHAT) with employee lifestyle risk factors, mental health issues and help-seeking intentions screened across eight industries. Subsequent data analysis involved descriptive statistics and chi-square tests. RESULTS: There were 1031 participants. Key stressors were work (30%), family (19%), money (14%) and interpersonal issues (5%). Approximately 18, 9 and 9% of participants were smokers, drinkers and gamblers, respectively, and only 51% exercised regularly. Depressive and anxiety symptoms were reported by 24 and 31% of employees, respectively. Issues for which they wanted immediate help were interpersonal abuse (16%), anxiety (15%), anger control (14%) and depression (14%). Employees with higher educational attainment were less likely to smoke, drink and gamble than those with lower attainment. Lifestyle and mental health status were not associated with income. Employees in construction and hotel industries smoked more and those in manufacturing drank more than those in other industries. CONCLUSIONS: Physical and mental health of Hong Kong employees are concerning. Although employee assistance programmes are common among large companies, initiation of proactive engagement approaches, reaching out to those employees in need and unlikely to seek help for mental health issues, may be useful.

Attitudes towards suicide following an undergraduate suicide prevention module: experience of medical students in Hong Kong.

OBJECTIVES: To explore qualitative and quantitative changes in attitudes and experiences of medical students following a special study suicide prevention module. DESIGN: Pilot study. SETTING: The University of Hong Kong, Hong Kong. PARTICIPANTS: A 2-week intensive special studies module was delivered to third- and fourth-year medical students in June 2011. The module was elective and involved several modes of teaching. All students filled the Chinese Attitude toward Suicide Questionnaire before and after the course. They also provided written feedback about the module experience. Three students participated in in-depth interviews. RESULTS: In all, 22 students aged 20 to 23 years enrolled in the special studies module; 15 (68%) of whom were male and only one was married. Positive trends were noted in attitudes towards suicide following the participation in the special studies module, namely, reduced negative appraisal of suicide, reduced stigmatisation of the phenomena, and increased sensitivity to suicide-related facts. Feedback of the students suggested inclusion of this module into the main medical curriculum, increased confidence in dealing with issues related to suicide, and appreciation of skills focusing on interviewing in patients. Overall the module was well received by medical students. CONCLUSIONS: A suicide prevention training module seems to have been valued by students and lead to positive attitudes towards understanding suicide. Adopting this initiative as a suicide prevention strategy warrants further exploration.

Suicides by jumping from iconic bridges in Hong Kong.

BACKGROUND: Three bridges in Hong Kong have become iconic sites for suicide since their openings 11 years ago. AIMS: This retrospective record-based study aimed to examine suicides by jumping from a group of three iconic bridges in Hong Kong, and to explore potential preventive strategies on these bridges to prevent future suicide. METHODS: We examined the Coroner's files of 12 people who killed themselves by jumping from the bridges between 1997 and 2007. We also examined the Coroner's files of other suicides in 2003, and compared them with the bridge suicides. RESULTS: The majority of the suicides were male, middle-age (40-59 years), married or cohabiting, not living alone, employed or self-employed, and in financial difficulty. None of these cases had a reported psychiatric diagnosis or psychiatric care history, and only one case had a history of suicidal attempt. Compared with other suicides in Hong Kong, the bridge jumpers were more likely to be younger, holding a job, indebted, free from a psychiatric and attempt history, and to leave a suicide note (p < .05). The bridge suicide cases in Hong Kong also appeared to be different from the profiles of bridge jumpers in other countries. CONCLUSIONS: Erection of an effective safety barrier has been found to prevent bridge suicides in many countries. Given the different characteristics of bridge jumpers in Hong Kong and the technical difficulties, more innovative ways may be needed to prevent suicides by such means. Potential prevention measures are discussed and, hopefully, will better inform the future design and development of bridges of significance.

MultiPriDe: automated batch development of quantitative real-time PCR primers.

Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) is a commonly employed gene expression quantification technique. This requires the development of appropriately targeted oligonucleotide primers, which necessitates the identification of ideal amplicons, development of optimized oligonucleotide sequences under most favorable pre-determined reaction conditions, and management of the resultant target-oligonucleotide pair information for each gene to be studied. The Primer3 utility exists for development of oligonucleotide primers and fills that role effectively. However, the manual process of identifying target sites and individually generating primers is inefficient and prone to user-introduced error, especially when a large number of genes are to be examined. We have developed MultiPriDe (Multiple Primer Design), a Perl utility that accepts batch lists of Gene database identifiers, collects available intron and exon position data critical to qRT-PCR primer development, and supplies these sites as identified targets for the Primer3 utility. This automated 'gene to primer' procedure is coupled with a set of optimized hybridization conditions used by the Primer3 utility to maximize successful primer design. MultiPriDe and assembled repeat libraries are available upon request. Please direct requests to aziesel@emory.edu.

The frequency of pre-core gene mutations in chronic hepatitis B infection: a study of Malaysian subjects.

A retrospective study was carried out to determine the frequency of the pre-core stop codon mutant virus in a group of chronic hepatitis B carriers: 81 cases were considered [33 hepatits B e antigen (HBe) positive and 48 HBe negative]. All of the HBe positive cases had detectable viral DNA by hybridization analysis; in the case of the HBe negative cases, one third had detectable viral DNA by hybridization analysis and two thirds had HBV DNA detectable by polymerase chain reaction (PCR) amplification. Pre-core stop codon mutant detection was carried out on all specimens using allele-specific oligonucleotide hybridization following PCR amplification of the target sequence. The pre-core mutant was detected in 13/33 (39.4%) of HBe positive cases and in 32/48 (66.7%) of HBe negative cases. Sequence analysis was carried out on 8 of the 16 HBe negative specimens that did not carry the pre-core mutant virus to determine the molecular basis for the HBe minus phenotype in these cases: the 1762/1764 TA paired mutation in the second AT rich region of the core promoter was detected in five cases; a start codon mutation was detected in one case. The predominant mutation resulting in the HBe minus phenotype in our isolates was the 1896A pre-core ("pre-core stop codon") mutation; other mutations responsible for the phenotype included the core promoter paired mutation and pre-core start codon mutation. In view of the high frequency of the pre-core mutant virus, sequence analysis was performed to determine the virus genotype on the basis of the nucleotide sequence of codon 15. The sequences of 21 wild type virus (14 HBe positive and 7 HBe negative cases) were examined: 15 were found to be codon 15 CCT variants (71.4%); the frequency in the HBe positive group was 12/14 (85.7%), while that in the HBe negative group was 3/7 (42.9%). The high frequency of the codon 15 CCT variant in association with the frequent occurrence of the pre-core mutant in our isolates concurs with the results of other studies.

Identification and characterization of C6orf37, a novel candidate human retinal disease gene on chromosome 6q14.

We have identified a novel human gene, chromosome 6 open reading frame 37 (C6orf37), that is expressed in the retina and maps to human chromosome 6q14, a genomic region that harbors multiple retinal disease loci. The cDNA sequence contains an open reading frame of 1314 bp that encodes a 437-amino acid protein with a predicted molecular mass of 49.2 kDa. Northern blot analysis indicates that this gene is widely expressed, with preferential expression observed in the retina compared to other ocular tissues. The C6orf37 protein shares homology with putative proteins in R. norvegicus, M. musculus, D. melanogaster, and C. elegans, suggesting evolutionary conservation of function. Additional sequence analysis predicts that the C6orf37 gene product is a soluble, globular cytoplasmic protein containing several conserved phosphorylation sites. Furthermore, we have defined the genomic structure of this gene, which will enable its analysis as a candidate gene for chromosome 6q-associated inherited retinal disorders.

Nutritional support in critically ill patients with cancer.

Nutritional depletion is a common problem seen in critically ill patients with cancer and is associated with increased morbidity and mortality. Infection and injury activate a cascade of metabolic events that leads to a poor nutritional state and wasteful energy consumption. The goals of nutritional support entail minimizing starvation, preventing nutrient deficiencies, supporting or improving immune function, and facilitating tissue repair and wound healing. Further understanding of the metabolic changes of illness will improve effective regulation of the inflammatory events occurring in critically ill patients. Multiple clinical parameters are available to assess the nutritional status in critically ill patients, but no standard recommendations can be made at this time. The use of these parameters can be appropriate, provided that their limitations are understood clearly. The development and standardization of objective parameters to identify patients at risk or with subclinical malnutrition are needed. Enteral and parenteral feedings are safe and effective methods to deliver nutrients to critically ill patients with cancer who are unable to ingest adequate amounts orally. Early nutritional support should be instituted in the appropriate clinical setting. Specialized nutritional solutions and supplements require careful consideration in patients with renal, hepatic, cardiac, or pulmonary disorders. The unselective use of nutritional support is not indicated in well-nourished patients with cancer undergoing surgery, chemotherapy, or radiotherapy in whom adequate oral intake is anticipated. Nutritional support remains an important adjunctive therapy in the overall management of critically ill patients. Continued clinical investigations in nutrition are necessary to identify other groups of patients who can benefit from nutritional interventions.

ortho-substituted PCB95 alters intracellular calcium signaling and causes cellular acidification in PC12 cells by an immunophilin-dependent mechanism.

ortho-Substituted PCBs mobilize Ca2+ from isolated brain microsomes by interaction with FKBP12/RyR complexes. Investigation into the cellular importance of this mechanism was undertaken using PC12 cells by fluoroimaging the actions of specific PCB congeners on [Ca2+]i and pH. RyR and IP3R share a common intracellular Ca2+ store in PC12 cells. Perfusion of nM to low microM PCB95 caused a transient rise of [Ca2+]i that was not completely dependent on extracellular Ca2+. Pre-incubation of the cells with ryanodine or FK506 completely eliminated PCB95 responses, suggesting a primary action on the FKPP12/RyR-sensitive store. PCB95, but not PCB126, induced a gradual decrease in cytosolic pH that could be completely eliminated by FK506 pre-incubation of the cells. Direct respiration measurement using isolated brain mitochondria demonstrated that neither of the PCBs directly altered any stage of mitochondrial respiration. These results revealed that PCB95 disrupts intracellular Ca2+ signaling in PC12 cells by interaction with the FKBP12/RyR complex that in turn accelerated cellular metabolism, possibly affecting signaling between ER and mitochondria. Since ortho-substituted PCBs have been shown to be neurotoxic and may affect neurodevelopment, studies on the molecular mechanism by which they alter cellular signaling may provide valuable information on the physiological roles of FKPB12 and RyR on neuronal functions.

A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy.

Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration characterized by decreased visual acuity, macular atrophy and extensive fundus flecks. Genetic mapping data suggest that mutations in a single gene may be responsible for both conditions, already known to bear clinical resemblance. Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photoreceptor-specific gene, ELOVL4, in all affected members of STGD3 and adMD families. Bioinformatic analysis of ELOVL4 revealed that it has homology to a group of yeast proteins that function in the biosynthesis of very long chain fatty acids. Our results are therefore the first to implicate the biosynthesis of fatty acids in the pathogenesis of inherited macular degeneration.

A buyer-seller watermarking protocol.

Digital watermarks have previously been proposed for the purposes of copy protection and copy deterrence for multimedia content. In copy deterrence, a content owner (seller) inserts a unique watermark into a copy of the content before it is sold to a buyer. If the buyer sells unauthorized copies of the watermarked content, then these copies can be traced to the unlawful reseller (original buyer) using a watermark detection algorithm. One problem with such an approach is that the original buyer whose watermark has been found on unauthorized copies can claim that the unauthorized copy was created or caused (for example, by a security breach) by the original seller. In this paper, we propose an interactive buyer-seller protocol for invisible watermarking in which the seller does not get to know the exact watermarked copy that the buyer receives. Hence the seller cannot create copies of the original content containing the buyer's watermark. In cases where the seller finds an unauthorized copy, the seller can identify the buyer from a watermark in the unauthorized copy and furthermore the seller can prove this fact to a third party using a dispute resolution protocol. This prevents the buyer from claiming that an unauthorized copy may have originated from the seller.

Secret and public key image watermarking schemes for image authentication and ownership verification.

We describe a watermarking scheme for ownership verification and authentication. Depending on the desire of the user, the watermark can be either visible or invisible. The scheme can detect any modification made to the image and indicate the specific locations that have been modified. If the correct key is specified in the watermark extraction procedure, then an output image is returned showing a proper watermark, indicating the image is authentic and has not been changed since the insertion of the watermark. Any modification would be reflected in a corresponding error in the watermark. If the key is incorrect, or if the image was not watermarked, or if the watermarked image is cropped, the watermark extraction algorithm will return an image that resembles random noise. Since it requires a user key during both the insertion and the extraction procedures, it is not possible for an unauthorized user to insert a new watermark or alter the existing watermark so that the resulting image will pass the test. We present secret key and public key versions of the technique.

Autosomal dominant Stargardt-like macular dystrophy segregating in a large Canadian family.

BACKGROUND: Inherited macular dystrophies account for a major fraction of the cases of retinal degenerative disease that lead to permanent blindness. We describe the clinical and genetic findings in a Canadian family with a form of macular dystrophy resembling autosomal dominant Stargardt-like macular dystrophy. METHODS: Standard ophthalmologic examinations were performed in members of a single five-generation Alberta family. Tests of visual acuity and colour vision, fundus photography, fluorescein angiography and electroretinography were performed in 15 affected people. Blood was collected from 24 family members, and DNA was extracted for genotyping. Genetic linkage analysis was performed using polymorphic short tandem repeat microsatellite markers located on chromosome 6q, a region containing loci for several macular disorders. RESULTS: Affected family members display clinical characteristics resembling autosomal dominant Stargardt-like macular dystrophy, previously assigned to chromosome 6q (STGD3). Linkage analysis generated a peak lod score of 5.50 at an estimated recombination fraction of 0.00 for marker locus D6S300. INTERPRETATION: The family described has an autosomal dominant macular dystrophy that resembles Stargardt-like macular dystrophy. The disease locus for this family maps to an interval on chromosome 6q that overlaps that for STGD3 and other retinal dystrophy loci. These findings provide further evidence that human chromosome 6q represents a "hot spot" for retinal disorders.

Antithrombotic and hemostatic capacity of factor Xa versus thrombin inhibitors in models of venous and arteriovenous thrombosis.

Thrombin plays a central role in venous and arterial thrombosis. We utilized two different rabbit models of in vivo thrombosis to investigate the effect of inhibitors of thrombin generation and thrombin activity. The agents tested were specific inhibitors of factor Xa (fXa) [N2-[(phenylmethyl)sulfonyl]-D-arginyl-N-[(1S)-4-[(aminoiminomethyl++ +)a mino]-1-(2-thiazolylcarbonyl)butyl]-glycinamide (C921-78)] and thrombin [D-phenylalanyl-N-[4-[(aminoiminomethyl)amino]-1-(chloroacetyl)but yl]-L-prolinamide (PPACK)], as well as drugs that affect both thrombin and fXa, unfractionated and low molecular weight (enoxaparin) heparin. The agents administered as constant intravenous infusion were evaluated for antithrombotic efficacy in anesthetized rabbits. All four agents were capable of dose dependent inhibition of thrombosis in venous and arteriovenous thrombosis models. However, due to the more aggressive nature of thrombotic stimulation in the arteriovenous shunt model, complete cessation of thrombus growth was not achieved for any of the agents at the doses tested. Comparison between the agents focused on the differences in extension of coagulation parameters (activated partial thromboplastin time, prothrombin time, thrombin clotting time), changes in hematological parameters, and extension of rabbit cuticle bleeding time at doses required to produce maximum inhibition in the thrombosis models. In the venous thrombosis model at the maximally effective dose, C921-78 had minimal extension of ex vivo clotting parameters, while enoxaparin and unfractionated heparin demonstrated a two to sevenfold increase in activated partial thromboplastin times, and PPACK had a threefold extension of thrombin clotting times. In addition, unlike the other three agents, which exhibited no significant changes in hematological parameters, PPACK demonstrated dose dependent thrombocytopenia. A standardized cuticle bleeding time was used as a measure of perturbation of hemostasis. The agents were evaluated for significant increases in bleeding time at doses up to eight times that needed to completely inhibit venous thrombus formation. Unfractionated heparin displayed a significant bleeding time effect at the dose required to inhibit venous thrombosis (100 u/kg+2 u/kg/min). Enoxaparin and PPACK caused significant bleeding time extensions at four times the fully efficacious venous dose (800 u/kg+8 u/kg/min and 30 microg/kg/min). By contrast, C921-78 did not significantly increase bleeding time even at eight times the maximally effective dose (240 microg/kg+7.2 microg/kg/min). Our results demonstrate that specific inhibition of fXa can be utilized to derive potent antithrombotic activity without disrupting extravascular hemostasis.

The utility of open lung biopsy in patients with hematologic malignancies.

The yield and impact of open lung biopsies in patients with hematologic malignancies and unexplained pulmonary processes were assessed and analyzed to determine factors that affected the yield. Records of 63 patients with hematologic malignancy, who underwent 67 open lung biopsies for diagnosis of an unknown pulmonary process from 1996 to 1998 at Memorial Sloan-Kettering Cancer Center, were retrospectively reviewed. A specific diagnosis was found in 41 (62%) of the biopsies. Changes in therapy were made in 37 (57%) of patients after biopsy results, but in 69% of those with a specific diagnosis. Survival at 30 and 90 d was increased in those with specific rather than a nonspecific pulmonary diagnosis. The factor most predictive of finding a specific diagnosis was the presence of a focal rather than a diffuse radiographic abnormality (79% versus 36%, p = 0.003). Neutropenic patients or those on mechanical ventilation had a low chance of finding a specific diagnosis. Having received pulmonary toxic chemotherapy in the 6 mo before the biopsy was associated with finding a nonspecific lung injury. Specific pulmonary diagnoses found were inflammatory diseases in 23% of cases, infections in 21%, and malignancy in 18%. Bronchiolitis obliterans with organizing pneumonia (BOOP) was the most common inflammatory disorder and fungi and bacteria were the most frequent infectious pathogens. Complications occurred in 13% of the biopsies, including five patients who required mechanical ventilation post-procedure; one death was associated with the biopsy. The risk was increased in those with less than 50,000 platelets. Complications were similar with video-assisted thoracoscopy (VATS) compared with thoracotomy. We conclude that open lung biopsy in patients with hematologic malignancy has a significant yield and impact on management of patients with hematologic malignancy.

The effect of varying inspiratory flow waveforms on pulmonary mechanics in critically ill patients.

PURPOSE: Ten mechanically ventilated patients were evaluated to determine the effect of three different inspiratory flow patterns on pulmonary mechanics. MATERIALS AND METHODS: Ten consecutive mechanically ventilated critically ill patients with acute respiratory failure admitted to the intensive care unit were evaluated to assess the effects of decelerating, square, and sine waveforms on pulmonary mechanics. The variables measured were peak airway pressure (PaW), pleural pressure (Ppl), change in peak airway pressure (dPaW), inspiration time/total ventilation cycle time (Vi/tot), dynamic compliance (Cdyn), respiratory rate (RR), minute ventilation (Ve), and work of breathing (WOB). RESULTS: The PaW, Ppl, and dPaW (cm H2O) were significantly lower using the decelerating inspiratory flow waveform (P<.05) compared with sine or square waveform patterns. Ti/Ttot was also lower with the decelerating waveform (P<.05) with better dynamic compliance compared with the other waveforms (P<.10). CONCLUSIONS: These results indicate that critically ill mechanically ventilated patients show improved respiratory mechanics with decelerating inspiratory waveform that may have beneficial clinical implication.

Inhibition of factor Xa by a peptidyl-alpha-ketothiazole involves two steps. Evidence for a stabilizing conformational change.

Recently, peptidylketothiazoles have been shown to be potent inhibitors of proteases, but the details of the interaction have not yet been studied. In the work presented here, the interaction of factor Xa, a coagulation protease, with the transition state inhibitor BnSO(2)-D-Arg-Gly-Arg-ketothiazole (C921-78) is characterized. C921-78 is a tight and selective inhibitor of the coagulation protease factor Xa (K(d) = 14 pM). The hydrolytic activity of factor Xa was inhibited by C921-78 in a time-dependent manner. The rate-limiting step of the bimolecular combination of inhibitor and enzyme was competitive with the substrate. Conversely, the inhibitor could be displaced from the active site of the enzyme after exposure of the preformed complex to an excess of substrate or to the active site inhibitor dansyl-Glu-Gly-Arg-chloromethyl ketone (DEGR-CMK) in a slow reaction. The formation of the C921-78-factor Xa complex resulted in a 60% increase in the magnitude of the fluorescence emission spectrum. Rapid mixing of the enzyme and inhibitor produces a monophasic fluorescence increase, compatible with spectral transition in a single step. The rate constant for this reaction increased hyperbolically with the concentration of C921-78, but the amplitude remained constant. These results are consistent with the initial formation of an enzyme-inhibitor complex (EI), followed by a unimolecular conversion of EI to EI linked to a spectral transition. The rate constants of the isomerization provide an estimate of 300000-fold stabilization. Thus, the inhibition of factor Xa by C921-78 follows a mechanism similar to that described classically for slow tight binding inhibitors. However, the two steps of the reaction cannot be kinetically separated by the rapid equilibrium assumption, and therefore, the formation of EI is partially rate-limiting, too. The driving energy for the unusually fast isomerization step may result from the highly favorable interactions of the inhibitor in the primary binding site.

Acute effect of nicotine patch on gastric emptying of liquid and solid contents in healthy subjects.

The effect of nicotine on gastric emptying remains controversial. Gastric emptying is delayed in chronic smokers after smoking high-dose nicotine cigarettes, but it is unchanged after chewing nicotine gums. No information is available on the effect of transdermal nicotine patches on the gastric emptying of solid and liquid contents in healthy nonsmokers. Our objective was to prospectively evaluate the effect of the nicotine patch on gastric emptying of liquid and solid contents in healthy nonsmokers. Ten healthy nonsmoking volunteers underwent a baseline dual-isotope gastric scintigraphy with [111In]-diethylenetriaminepantaacetic acid (DTPA) and [99mTc]sulfur colloid isotopes to evaluate prospectively the gastric emptying of liquid and solid contents, respectively. The gastric scintigraphy was repeated after placing a transdermal nicotine patch (Habitrol) for 12 hr designed to deliver 14 mg of nicotine per day. Plasma nicotine level was measured prior to baseline gastric scintigraphy and after 12 hr placing the nicotine patch. Plasma nicotine was absent in all subjects at baseline and but was significantly elevated after 12 hr of nicotine patch (P < 0.009). The mean half-emptying times (T1/2) for the gastric emptying of liquids before and after nicotine patch placement were 31.2+/-23.3 and 25.6+/-8.4 min, respectively (P = 0.498). The mean T1/2s for the gastric emptying of solids before and after nicotine patch placement were 70.1+/-34.0 and 59.7+/-31.4 min, respectively (P = 0.202). There was no correlation between the plasma nicotine level and gastric emptying of liquid and solid contents (correlation coefficient = -0.23 and -0.01, respectively). In conclusion, acute transdermal delivery of nicotine does not affect the gastric emptying of solid and liquid contents in healthy nonsmoking subjects.

How to deal with chronic constipation. A stepwise method of establishing and treating the source of the problem.

Chronic constipation is a common medical complaint encountered often in a primary care setting. Most patients can be treated successfully with simple measures, including education, bowel habit training, increased fluid and fiber intake, and use of laxatives. Chronic constipation is usually considered idiopathic, but secondary causes should be excluded. In about 1% of patients with severe, intractable constipation, further diagnostic testing (e.g., endoscopy, colonic transit study) is needed. Patients with colonic inertia can be treated with judicious use of laxatives, but surgery may be necessary in a few cases. Patients with outlet inertia should be referred for biofeedback treatment.