GSK3ß: A plausible molecular target in the cytokinemodulating effect of exogenous insulin in a murine model of malarial infection.

Malaria is a life-threatening disease caused by the Plasmodium sp. parasite. Infection results in heightened pro-inflammatory response which contributes to the pathophysiology of the disease. To mitigate the overwhelming cytokine response, host-directed therapy is a plausible approach. Glycogen synthase kinase-3ß (GSK3ß), a serine/threonine kinase plays a pivotal role in the regulation of inflammatory response during pathogenic infections. The present study was conducted to investigate the chemo-suppressive and cytokine-modulating effects of insulin administration in malaria-infected mice and the involvement of GSK3ß. Intraperitoneal administrations of 0.3 and 0.5 U/kg body weight insulin each for four consecutive days into Plasmodium berghei NK65 (PbN)-infected mice resulted in chemo-suppression exceeding 60% and improved median survival time of infected mice (20.5 days and 19 days respectively compared to 15.5 days for non-treated control). Western analysis revealed that pGSK3ß (Ser9) intensity in brain samples from insulin-treated (0.3 and 0.5 U/kg body weight) infected mice each were 0.6 and 2.2 times respectively than that in control. In liver samples, pGSK3ß (Ser9) intensity from insulin-treated infected mice were significantly higher (4.8 and 16.1 fold for 0.3 and 0.5 U/kg bw respectively) than that in control. Insulin administration decreased both brain and liver pNF-κB p65 (Ser536) intensities (to 0.8 and 0.6 times for 0.3 U/kg bw insulin; and to 0.2 and 0.1 times for 0.5 U/kg bw insulin respectively compared to control). Insulin treatment (0.5 U/kg bw) also significantly decreased the serum levels of pro-inflammatory cytokines (TNF-α (3.3 times) and IFN-γ (4.9 times)) whilst significantly increasing the levels of anti-inflammatory cytokines (IL-4 (4.9 fold) and IL-10 (2.1 fold)) in PbN-infected mice. Results from this study demonstrated that the cytokinemodulating effects of insulin at least in part involve inhibition of GSK3ß and consequent inhibition of the activation of NF-κB p65 suggesting insulin as a potential adjunctive therapeutic for malaria.

GSK3β: A plausible molecular target in the cytokinemodulating effect of exogenous insulin in a murine model of malarial infection

@# Malaria is a life-threatening disease caused by the Plasmodium sp. parasite. Infection results in heightened pro-inflammatory response which contributes to the pathophysiology of the disease. To mitigate the overwhelming cytokine response, host-directed therapy is a plausible approach. Glycogen synthase kinase-3β (GSK3β), a serine/threonine kinase plays a pivotal role in the regulation of inflammatory response during pathogenic infections. The present study was conducted to investigate the chemo-suppressive and cytokine-modulating effects of insulin administration in malaria-infected mice and the involvement of GSK3β. Intraperitoneal administrations of 0.3 and 0.5 U/kg body weight insulin each for four consecutive days into Plasmodium berghei NK65 (PbN)-infected mice resulted in chemo-suppression exceeding 60% and improved median survival time of infected mice (20.5 days and 19 days respectively compared to 15.5 days for non-treated control). Western analysis revealed that pGSK3β (Ser9) intensity in brain samples from insulin-treated (0.3 and 0.5 U/kg body weight) infected mice each were 0.6 and 2.2 times respectively than that in control. In liver samples, pGSK3β (Ser9) intensity from insulin-treated infected mice were significantly higher (4.8 and 16.1 fold for 0.3 and 0.5 U/kg bw respectively) than that in control. Insulin administration decreased both brain and liver pNF-κB p65 (Ser536) intensities (to 0.8 and 0.6 times for 0.3 U/kg bw insulin; and to 0.2 and 0.1 times for 0.5 U/kg bw insulin respectively compared to control). Insulin treatment (0.5 U/kg bw) also significantly decreased the serum levels of pro-inflammatory cytokines (TNF-α (3.3 times) and IFN-γ (4.9 times)) whilst significantly increasing the levels of anti-inflammatory cytokines (IL-4 (4.9 fold) and IL-10 (2.1 fold)) in PbN-infected mice. Results from this study demonstrated that the cytokinemodulating effects of insulin at least in part involve inhibition of GSK3β and consequent inhibition of the activation of NF-κB p65 suggesting insulin as a potential adjunctive therapeutic for malaria.

Emergence of Carbapenem-Resistant Acinetobacter baumannii in Nursing Homes With High Background Rates of MRSA Colonization.

Carbapenem-resistant Acinetobacter baumannii (CRAB) with diverse multilocus sequence typing emerged among our nursing home residents (6.5%) with a high background rate of MRSA (32.2%). Rectal swabs yielded a higher rate of CRAB detection than axillary or nasal swabs. Bed-bound status, use of adult diapers, and nasogastric tube were risk factors for CRAB colonization. Infect Control Hosp Epidemiol 2016;37:983-986.

Mortality and health services utilisation among older people with advanced cognitive impairment living in residential care homes.

OBJECTIVES: To study the demography, clinical characteristics, service utilisation, mortality, and predictors of mortality in older residential care home residents with advanced cognitive impairment. DESIGN: Cohort longitudinal study. SETTING: Residential care homes for the elderly in Hong Kong West. PARTICIPANTS: Residents of such homes aged 65 years or more with advanced cognitive impairment. RESULTS: In all, 312 such residential care home residents (71 men and 241 women) were studied. Their mean age was 88 (standard deviation, 8) years and their mean Barthel Index 20 score was 1.5 (standard deviation, 2.0). In all, 164 (53%) were receiving enteral feeding. Nearly all of them had urinary and bowel incontinence. Apart from Community Geriatric Assessment Team clinics, 119 (38%) of the residents attended other clinics outside their residential care homes. In all, 107 (34%) died within 1 year; those who died within 1 year used significantly more emergency and hospital services (P<0.001), and utilised more services from community care nurses for wound care (P=0.001), enteral feeding tube care (P=0.018), and urinary catheter care (P<0.001). Independent risk factors for 1-year mortality were active pressure sores (P=0.0037), enteral feeding (P=0.008), having a urinary catheter (P=0.0036), and suffering from chronic obstructive pulmonary disease (P=0.011). A history of pneumococcal vaccination was protective with respect to 1-year mortality (P=0.004). CONCLUSION: Residents of residential care homes for the elderly with advanced cognitive impairment were frail, exhibited multiple co-morbidities and high mortality. They were frequent users of out-patient, emergency, and in-patient services. The development of end-of-life care services in residential care homes for the elderly is an important need for this group of elderly.

Wideband wavelength conversion of 16 Gbaud 16-QAM and 5 Gbaud 64-QAM signals in a semiconductor optical amplifier.

We demonstrate wavelength conversion based on four-wave mixing in a semiconductor optical amplifier of signals with quadrature amplitude modulation (QAM). We first demonstrate wavelength conversion of 16 Gbaud 16-QAM signals over the entire C-band using two co-polarized pumps with low power penalty at the forward error correction threshold (FEC) for a wide range of input optical-signal-to-noise-ratio (OSNR). We also demonstrate for the first time wavelength conversion of 5 Gbaud 64-QAM signals in a semiconductor optical amplifier with bit-error rate below the FEC threshold over the entire C-band and investigate the dependence of the power penalty on input OSNR with a single pump configuration.

Bilinear common spatial pattern for single-trial ERP-based rapid serial visual presentation triage.

Common spatial pattern (CSP) analysis is a useful tool for the feature extraction of event-related potentials (ERP). However, CSP is essentially time invariant, and thus unable to exploit the temporal information of ERP. This paper proposes a variant of CSP, namely bilinear common spatial pattern (BCSP), which is capable of accommodating both spatial and temporal information. BCSP generalizes CSP through iteratively optimizing bilinear filters. These bilinear filters constitute a spatio-temporal subspace in which the separation between two conditions is maximized. The method is unique in the sense that it is mathematically intuitive and simple, as all the bilinear filters are obtained by maximizing the power ratio as CSP does. The proposed method was evaluated on 20 subjects' ERP data collected in rapid serial visual presentation triage experiments. The results show that BCSP achieved significantly higher average test accuracy (12.3% higher, p < 0.001).

Immunogenicity of a truncated enterovirus 71 VP1 protein fused to a Newcastle disease virus nucleocapsid protein fragment in mice.

Enterovirus 71 (EV71) is one of the viruses that cause hand, foot and mouth disease. Its viral capsid protein 1 (VP1), which contains many neutralization epitopes, is an ideal target for vaccine development. Recently, we reported the induction of a strong immune response in rabbits to a truncated VP1 fragment (Nt-VP1t) displayed on a recombinant Newcastle disease virus (NDV) capsid protein. Protective efficacy of this vaccine, however, can only be tested in mice, since all EV71 animal models thus far were developed in mouse systems. In this study, we evaluated the type of immune responses against the protein developed by adult BALB/c mice. Nt-VP1t protein induced high levels of VP1 IgG antibody production in mice. Purified VP1 antigen stimulated activation, proliferation and differentiation of splenocytes harvested from these mice. They also produced significant levels of IFN-γ, a Th1-related cytokine. Taken together, Nt-VP1t protein is a potent immunogen in adult mice and our findings provide the data needed for testing of its protective efficacy in mouse models of EV71 infections.

Differential proteomic responses in hepatopancreas and adductor muscles of the green-lipped mussel Perna viridis to stresses induced by cadmium and hydrogen peroxide.

This study aimed to reveal the proteomic responses in the hepatopancreas and adductor muscle of a common biomonitor, Perna viridis after 14-day exposure to two model chemicals, cadmium (Cd; a toxic metal) and hydrogen peroxide (H(2)O(2); a pro-oxidant), using two-dimensional gel electrophoresis coupled with multivariate statistical analyses. Unique sets of tissue-specific protein expression signatures were revealed corresponding to the two treatment groups. In the hepatopancreas, 15 and 2 spots responded to Cd and H(2)O(2) treatments respectively. 6 and 7 spots were differentially expressed in the adductor muscle for Cd and H(2)O(2) treatments, respectively. 15 differentially expressed spots were successfully identified by MALDI-TOF/TOF MS analysis. These proteins are involved in glycolysis, amino acid metabolism, energy homeostasis, oxidative stress response, redox homeostasis and protein folding, heat-shock response, and muscle contraction modulation. This is the first time, to have demonstrated that Cd exposure not only leads to substantial oxidative stress but also results in endoplasmic reticulum stress in hepatopancreas of the mussel. Such notable stress responses may be attributable to high Cd accumulation in this tissue. Our results suggested that investigations on these stress-associated protein changes could be used as a new and complementary approach in pollution monitoring by this popular biomonitor species.

Isolation and characterization of microsatellite markers from the limpet Cellana grata.

This note describes the development of nine polymorphic microsatellite loci in the limpet Cellana grata to investigate population structure and cohort variation in this species. The number of alleles ranged from seven to 22 and observed heterozygosity ranged from 0.62 to 0.95. Deviation from the Hardy-Weinberg equilibrium was detected in two loci, both as a result of heterozygote deficiency. Null alleles were detected in one of these loci. These genetic markers will be used to investigate the genetic structure of C. grata populations, as well as variation among cohorts of this common intertidal species.

Trace metals and organochlorines in the bamboo shark Chiloscyllium plagiosum from the southern waters of Hong Kong, China.

The bamboo shark Chiloscyllium plagiosum is an abundant benthic species along the shallow continental shelf of Southeast Asia. It is commonly taken by fishermen in China, India, Taiwan and Thailand for human consumption. This study measured trace metal and organochlorine concentrations in C. plagiosum collected from the southern waters of Hong Kong, China. Metals (Ag, Cd, Cr, Cu, Mn, Ni, Pb and Zn) were measured in three different tissues: dorsal muscle, spleen and liver. Polychlorinated biphenyls (PCBs) and chlorinated pesticides in the dorsal muscle were identified and quantified using gas chromatography. Metal concentrations varied among the three different tissues, with liver having higher levels of Ag and Cd, and spleen possessing higher levels of Cu and Mn. Both Ni and Pb in all tissues were below the detection limit. Tissue concentrations of Cr, Cu, Mn and Zn generally decreased with increasing body weight whilst no significant concentration-size relationship was found for other metals. In muscle tissues, total PCBs ranged from 1.056-4.771 ng/g (wet wt.) with a median of 1.801 ng/g, while total DDTs ranged from 0.602-23.55 ng/g with a median of 1.109 ng/g, in which p,p'-DDE was the predominant metabolite. Levels of total hexachlorohexanes and cyclodienes were low. The pesticide p,p'-DDT was the only compound found to be positively correlated with body weight, indicating temporal bioaccumulation of this compound. Zn concentrations in the muscle of C. plagiosum were comparatively higher than recorded in other shark species, however, concentrations of other metals and organochlorines were relatively low. C. plagiosum feeds primarily on polychaetes, shrimps and small fishes, and thus is unlikely to contain levels of contaminants of human health concern.

Ecological risk assessments of endocrine disrupting organotin compounds using marine neogastropods in Hong Kong.

As active ingredients of anti-fouling paints that are widely used on ship hulls, organotin compounds, in particular tributyltin (TBT), are well-known endocrine disruptors causing sex changes in marine organisms and widespread in coastal waters and sediments worldwide. In this study, a comprehensive ecological risk assessment (ERA) of organotins was conducted in Hong Kong waters through determining the imposex status, sex ratio and tissue burdens of these compounds in the neogastropods, Thais clavigera and Thais luteostoma collected from 29 coastal sites. We also investigated the historical trend of organotin effects on these gastropods, and performed a probabilistic ERA based on tissue burden of TBT in the animals. Our results demonstrated that imposex indices were positively correlated with the body burden of organotins in the gastropods. Across all sites, the sex ratio (female:male) decreased significantly with increasing imposex levels or tissue burden of organotins, implying that such pollutants can result in a male-biased population, potentially leading to local extinction in extreme cases. Based on the ERA, 5.4% of all populations of T. clavigera are at risk due to exposure to TBT; the risks include growth inhibition, impairment of immune functions and reduced fitness. Seriously impacted areas included Aberdeen, Repulse Bay, Butterfly Beach, Mui Wo and Ha Mei Wan. A comparison with historical data revealed that there had been some improvement in the areas with low marine traffic, and distant from the major harbour/port. This could partly be due to the restriction on the use of TBT on small vessels (<25m in length) since 1992. Nevertheless, the organotin contamination still remains severe in areas with high marine traffic or adjacent to large harbours/ports. In particular, the situation in the northeastern waters of Hong Kong has been getting worst since 1996 that is probably associated with the rapid development of the cargo container port at Yantian in China.

Malignant rhabdoid tumour of the oesophagus: a case report.

Malignant extrarenal rhabdoid tumour (MERT) of the gastrointestinal tract is rarely reported in the literature. This report describes the clinical and pathological features of a malignant rhabdoid tumour of the oesophagus in a Chinese man. Ivor-Lewis oesophagectomy had been performed. The tumour behaved aggressively and the patient died from disseminated malignancy one year later. This is only the second case report of a malignant rhabdoid tumour affecting the oesophagus.

End-of-life issues--preferences and choices of a group of elderly Chinese subjects attending a day care centre in Singapore.

INTRODUCTION: This was an exploratory study that was intended to provide a descriptive analysis of the choices and preferences of a group of elderly Chinese subjects attending a day care centre in Singapore with regard to end-of-life issues. MATERIALS AND METHODS: A semi-structured one-to-one interview was conducted to collect data from the subjects. Qualitative techniques were used to analyse the data. RESULTS: Forty-three subjects were interviewed. The median age was 71 years. There were more women than men (58.1% vs. 41.9%). The predominant religion was Buddhism/Taoism. 83.7% and 76.7% of the subjects preferred to be told of the diagnosis and prognosis of a terminal illness, respectively. The person most preferred to reveal the diagnosis was the attending doctor (60.5%). About 83.7% of the subjects have never heard of the Advanced Medical Directive Act, while 37.2% agreed that making an advanced directive would be necessary. Twenty-three (53.5%) would choose the doctor, while 15 (34.9%) would choose a family member as a surrogate decision-maker. Twenty-two (51.2%) thought that euthanasia should be allowed, while 15 (34.9%) disagreed. With regard to supportive measures at the end of life, 67.4% wanted cardiopulmonary resuscitation, 62.8% wanted artificial ventilation, 55.8% wanted nasogastric feeding, 65.1% wanted intravenous hydration and 41.9% wanted renal dialysis. CONCLUSION: There is a need for closer communication between older persons and their carers with regard to end-of-life care. The attending doctor appears to have an important role in this respect.

Detection of pre-S/S gene mutants in chronic hepatitis B carriers with concurrent hepatitis B surface antibody and hepatitis B surface antigen.

Hepatitis B virus (HBV) with various mutations has been reported. The frequency of the natural occurrence of such variants and whether the heterogeneity of these genomic regions correlates with a specific serologic pattern of concurrent hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were investigated. We analyzed the perS/S regions of HBV in six asymptomatic HBV carriers who were seropositive for both HBsAg and anti-HBs (group A), four hepatocellular carcinoma (HCC) patients with concurrent HBsAg and anti-HBs (group B), and five asymptomatic HBV carriers without anti-HBs as controls (group C). PreS/S regions of HBV-DNA were amplified by polymerase chain reaction (PCR), cloned, and sequenced. The results showed that, in some of the samples, a few deletions and numerous point mutations were presented in preS/S regions. One of the HBV carriers with anti-HBs (group A) and an HCC patient with anti-HBs (group B) had point mutations in the "a" determinant, resulting in conversion from Ile-126 of wild-type to Asn-126. The patients with anti-HBs (groups A and B) had a significantly greater divergence rate of amino acid for the preS/S gene compared with controls. Our results suggested that the HBV mutants observed in the preS/S gene may have led to changes in the immunogenicity of the viral particles, and thus influence the viral behavior and clinical course. Therefore, some HBV patients with concurrent HBsAg and anti-HBs may be HBV S mutants.

Suppression of hepatitis C virus by hepatitis B virus in coinfected patients at the National University Hospital of Singapore.

This study was carried out to compare hepatitis B virus (HBV) and hepatitis C virus (HCV) replicative states and to determine possible interference between HBV and HCV. One thousand and sixty-one consecutive patients seen at The Gastroenterology Division of the National University Hospital of Singapore between 1988 and 1995 were screened for HBV and HCV serological markers. Anti-HCV was tested using a second-generation enzyme-linked immunosorbent assay (ELISA) method. HCV-RNA was detected by a reverse-transcription polymerase chain reaction method (RT-PCR). Data were analyzed by either paired t-test or chi2 test. Two hundred and twenty-four patients were infected with HBV alone, while 117 patients were infected with HCV only. Thirty-one patients were coinfected with HBV and HCV. HCV-RNA was detected in 104 of the 117 HCV patients (88.9%), and in 12 of 29 coinfected patients (41.4%). Serum anti-HCV levels in the coinfected patients were lower than those in the HCV-infected patients. A significant difference for anti-HCV reactivity and HCV-RNA positivity was observed between HCV-infected patients and coinfected patients (P < 0.01). In contrast, HBV-DNA and hepatitis B envelope antigen (HBeAg) positive rates were similar in HBV carriers and patients coinfected with HBV and HCV. These results show a possible interaction between HBV and HCV life cycles, and suggest that HCV replication may be negatively affected by HBV.

Detection of Mycobacterium tuberculosis DNA using polymerase chain reaction in cutaneous tuberculosis and tuberculids.

BACKGROUND: The objective of this study was to explore the role of the polymerase chain reaction (PCR) fo the detection of Mycobacterium tuberculosis DNA as a diagnostic aid in cutaneous tuberculosis using routinely processed skin biopsy specimens. METHODS AND RESULTS: A wide range of clinical specimens representing different forms of cutaneous tuberculosis and so-called tuberculids were studied. A sensitive and specific PCR assay targeting the sequence IS6110 of Mycobacterium tuberculosis complex was used. The specimens were categorized as follows. 1 Acid-fast bacilli (AFB) positive on biopsy (nine specimens from seven patients who were immunocompromised). PCR was positive in five specimens. Of these, one specimen was culture positive and three specimens were culture negative. 2 AFB negative on biopsy: (a) tuberculosis verrucosa cutis (23 specimens); (b) lupus vulgaris (three specimens); (c) cutaneous tuberculosis clinically suspected (six specimens). PCR was negative in all specimens. 3 Tuberculids.' (a) erythema induratum/nodular vasculitis (20 specimens); (b) papulonecrotic tuberculid (two specimens); (c) erythema nodosum (20 specimens). PCR was negative in all specimens. CONCLUSIONS: The role of PCR in clinical dermatologic practice, at this stage, may be in differentiating between cutaneous tuberculosis and atypical mycobacterial infections in the context of an immunocompromised patient where AFB can be demonstrated on biopsy and cultures may be negative. In this clinical situation, PCR allows the prompt diagnosis and early institution of appropriate therapy. We have not found PCR to be a useful complement to the clinical and histologic diagnosis of "paucibacillary" forms of cutaneous tuberculosis.

The combination of omeprazole, amoxycillin, and clarithromycin eradicates Helicobacter pylori in 95% of patients---7 days of therapy is as good as 10 days.

More than half of the known Helicobacter pylori strains are resistant to metronidazole, according to previous Hong Kong studies. The response rates to treatment regimens that comprise metronidazole as one of the antimicrobial agents have usually been disappointing in cases involving metronidazole-resistant strains. The objective of this open cohort evaluation was to assess the efficacy of an alternative regimen that combines omeprazole with amoxycillin and clarithromycin in Helicobacter pylor-positive ulcer and non-ulcer patients in Hong Kong. Furthermore, we aimed to investigate if 7 days were as good as 10 days of therapy. We studied 186 Helicobacter pylor-positive subjects; 149 subjects received 7 days of combination therapy and 37 subjects received 10 days. Our results showed that the overall Helicobacter pylori eradication efficiency was identical (94.6%) for both treatments. The incidences of adverse effects were also very similar (16.8% versus 16.2%) and both treatments were well tolerated. Thus, we propose that omeprazole in combination with amoxycillin and clarithromycin should be considered as one of the first-line therapies for patients with Helicobacter pylor infection in Hong Kong.

Comparative usefulness of PCR in the detection of Mycobacterium tuberculosis in different clinical specimens.

The role of the polymerase chain reaction (PCR) in the diagnosis of tuberculosis in clinical practice remains to be defined; most results have been based on sputum samples. This study systematically compared the relative sensitivity and specificity of a single simplified method for different clinical samples. A wide range of clinical samples, including sputum, bronchoalveolar lavage fluid, cerebrospinal fluid, pleural fluid, gastric aspirate, pus and tissues (both fresh and paraffin-embedded) was tested. This method did not require routine DNA extraction before PCR, and consisted of an optimised single tube PCR amplification designed with different sets of time and temperature profiles. A total of 398 samples from 293 patients was studied. The sensitivity was 100% for all types of specimens, while the specificity ranged from 95% for sputum to 88% for bronchoalveolar lavage fluid and pleural fluid and to 85% for non-pulmonary specimens. This study showed that it was possible to employ a single simplified method with minor modifications for a wide range of specimens in clinical practice without loss of sensitivity and specificity.