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Objective: To evaluate the effectiveness and tolerability of lacosamide added to one or two antiepileptic drugs (AEDs) in the treatment of patients with brain tumor–related epilepsy (BTRE), and to evaluate patients’ global impression of change and quality of life (QoL). Methods: This was a prospective, multicenter, single-arm, noninterventional study with a 6-month observation period (EP0045; NCT02276053). Eligible patients (≥16 years old) had active BTRE secondary to low-grade glioma (World Health Organization grade 1 and 2) and were receiving treatment with one or two AEDs at baseline. Lacosamide was initiated by the treating physician in the course of routine clinical practice. Primary outcomes were 50% responders (≥50% reduction in focal seizure frequency from baseline) and Patient's Global Impression of Change (PGIC) at month 6. Secondary outcomes included seizure-free status and Clinical Global Impression of Change (CGIC) at month 6, change in QoL (5-Level EuroQol-5 Dimension Quality of Life Assessment) and symptom outcomes (MD Anderson Symptom Inventory–Brain Tumor) from baseline to month 6, and Kaplan-Meier estimated 6-month retention on lacosamide. Safety variables included adverse drug reactions (ADRs). Results: Patients were recruited from 24 sites in Europe. Ninety-three patients received lacosamide (mean [standard deviation] age = 44.5 [14.7] years; 50 [53.8%] male; median baseline focal seizure frequency = five seizures/28 days [range = 1-280]), of whom 79 (84.9%) completed the study. At 6 months, 66 of 86 (76.7%) patients were 50% responders and 30 of 86 (34.9%) were seizure-free. Improvements on PGIC were reported by 49 of 76 (64.5%) patients. Based on CGIC, 52 of 81 (64.2%) patients improved. QoL and symptoms outcome measures remained stable. Kaplan-Meier estimated 6-month retention rate was 86.0% (N = 93). Fifteen (16.1%) patients reported ADRs; four (4.3%) had ADRs leading to discontinuation (N = 93). Significance: Results of this prospective, noninterventional study suggest that add-on lacosamide is effective and generally well tolerated in patients with BTRE.

There is a paucity of data on the incidence, risk factors, and treatment of splanchnic vein thrombosis (SVT) in acute pancreatitis (AP).All AP admissions between 2018 and 2021 across North East of England were included. Anticoagulation was considered in the presence of superior mesenteric vein/portal vein (SMV/PV) thrombus or progressive splenic vein thrombus (SpVT). The impact of such a selective anticoagulation policy, on vein recanalisation rates and bleeding complications were explored.401 patients (median age 58) were admitted with AP. 109 patients (27.2%) developed SVT. The splenic vein in isolation was the most common site (n = 46) followed by SMV/PV (n = 36) and combined SMV/PV and SpVT (n = 27). On multivariate logistic regression alcohol aetiology (OR 2.64, 95% CI [1.43-5.01]) and50% necrosis of the pancreas (OR 14.6, 95% CI [1.43-383.9]) increased the risk of developing SVT. The rate of recanalization with anticoagulation was higher for PVT (66.7%; 42/63) than in SpVT (2/11; p = 0.003). 5/74 of anticoagulated patients developed bleeding complications while 0/35 patients not anticoagulated had bleeding complications (p = 0.4).The risk of SVT increases with AP severity and with extent of pancreatic necrosis. A selective anticoagulation policy for PVT and progressive SpVT in AP is associated with favourable outcomes with no increased risk of bleeding complications.

Background There is paucity of data on the incidence, risk factors and role of anticoagulation for splanchnic vein thrombosis (SVT) in acute pancreatitis (AP). Methods A retrospective review of AP admissions between 2018-2021 across North East England was undertaken. Data on demographics, etiology, severity of AP and SVT was collected. In addition, a selective anticoagulation policy for portal vein thrombosis (PVT) and progressive splenic vein thrombosis was explored. Results 401 patients were included with a mean age of 57.0 and M:F ratio of 1.6:1. 152 patients developed intestinal oedematous pancreatitis and 249 developed necrotising pancreatitis based on Revised Atlanta criteria (RAC). 109 patients (27.2%) developed SVT of which 27 developed a PVT and splenic vein thrombus, 36 PVT only and 46 splenic vein thrombus only. On univariate analysis, alcoholic aetiology, severe pancreatitis, necrotising pancreatitis with >50% necrosis and elevated CRP at 2 weeks were risk factors for developing SVT. On multivariable analysis, alcohol aetiology (OR 2.6, p = 0.002), and >50% pancreatic necrosis (OR 14.6,p = 0.048) increased the risk of developing SVT . 58 patients received anticoagulation for SVT, with a median duration of 90 days of anticoagulation. Recanalization rates were higher for PVT when compared to splenic vein thrombosis. 6 patients developing bleeding complications whilst on anticoagulation therapy. Conclusions A third of patients with AP develop SVT, particularly those with severe AP secondary to alcohol and with extensive pancreatic necrosis. A selective anticoagulation policy was associated with improved recanalization rates and fewer bleeding complications.

Background This systematic review explored the efficacy of different pain relief modalities used in the management of postoperative pain following pancreatoduodenectomy (PD) and distal pancreatectomy (DP) and impact on perioperative outcomes. Methods MEDLINE (OVID), Embase, Pubmed, Web of Science and CENTRAL databases were searched using PRISMA framework. Primary outcomes included pain on postoperative day 2 and 4 and respiratory morbidity. Secondary outcomes included operation time, bile leak, delayed gastric emptying, postoperative pancreatic fistula, length of stay, and opioid use. Results Five randomized controlled trials and seven retrospective cohort studies (1313 patients) were included in the systematic review. Studies compared epidural analgesia (EDA) (n = 845), patient controlled analgesia (PCA) (n = 425) and transabdominal wound catheters (TAWC) (n = 43). EDA versus PCA following PD was compared in eight studies (1004 patients) in the quantitative meta-analysis. Pain scores on day 2 (p = 0.19) and 4 (p = 0.18) and respiratory morbidity (p = 0.42) were comparable between EDA and PCA. Operative times, bile leak, delayed gastric emptying, pancreatic fistula, opioid use, and length of stay also were comparable between EDA and PCA. Pain scores and perioperative outcomes were comparable between EDA and PCA following DP and EDA and TAWC following PD. Conclusions EDA, PCA and TAWC are the most frequently used analgesic modalities in pancreatic surgery. Pain relief and other perioperative outcomes are comparable between them. Further larger randomized controlled trials are warranted to explore the relative merits of each analgesic modality on postoperative outcomes with emphasis on postoperative complications.

Background In elderly patients (≥65 years of age) with epilepsy who take medications for comorbid conditions, some antiepileptic drugs (AEDs) may alter the metabolism of other treatments and increase the risk of adverse consequences and healthcare utilisation. This analysis compares healthcare costs associated with enzyme-inducing AEDs (EIAEDs) and non-enzyme active AEDs (nEAAEDs) use in elderly patients with epilepsy. Methods This retrospective matched cohort study used the Clinical Practice Research Datalink (CPRD) of UK primary care medical records, linked to the Hospital Episode Statistics (HES) database. Selected patients with epilepsy were ≥ 65 years and prescribed an EIAED or nEAAED between 2001 and 2010 (index) after ≥1 year without AEDs (baseline) and followed until the first occurrence of the following: end of HES data coverage, end of GP registration, or death; practice’s up-to-standard status or addition of an AED belonging to another cohort or discontinuation of the last AED of that cohort. Propensity score matching reduced confounding factor effects between cohorts. Key outcomes included time to cohort treatment failure, time to index AED treatment failure, and direct healthcare costs in 2014 Pound Sterling (£) values. Results Overall, 1425 elderly patients were included: 964 with EIAEDs and 461 with nEAAEDs. At baseline, the EIAED cohort was older (mean age, 76.2 vs. 75.1 years) and a higher proportion were male. Baseline direct healthcare costs were similar. After matching (n = 210 each), and over the entire follow-up period, median monthly direct healthcare costs were higher for patients taking EIAEDs than nEAAEDs (£403 vs. £317; p = 0.0150, Mann-Whitney U). Costs were higher for patients remaining in the EIAED cohort after 3 follow-up years. The median time to cohort treatment failure for the EIAED cohort was 1110 days vs. 1175 days for the nEAAED cohort. Conclusion Newly treated elderly patients with epilepsy were more likely to be prescribed EIAEDs than nEAAEDs. In matched cohorts, elderly patients with epilepsy treated with EIAEDs had higher average total direct and epilepsy-related healthcare costs than nEAAED-treated patients; this difference was greater than previously reported in the overall adult population. Changing treatment practices could improve patient care and reduce costs.

Purpose of the study: The term, Kong Girls is new in Hong Kong in the past ten years. The purpose of this research is to suggest reasons behind the Kong Girls phenomenon and to explore whether this will continue to be a factor for Hong Kong men marrying Mainland women. Methodology: Seven interviews with typical Hong Kong Kong Girls were conducted within a similar period of time in 2015. One non-Kong-Girl was also interviewed as a control. Main Findings: findings of this research indicate that the Kong Girls phenomenon may be a social problem in the long run and Hong Kong men have to continue to find their wives outside Hong Kong if traditional thinking is not to be changed. If Hong Kong women continue to be Kong Girls, both genders may not be able to find their partner locally at their home city. Implications: social studies, psychology, gender issues Novelty/Originality of this study: This article helps explain why Hong Kong women prefer to marry non-Hong Kong men or choose to remain single. This is first of its kind study.

The South China Sea has long been a source of regional tension, and disputes have heated up significantly in recent years. Disagreements over competing territorial sovereignty and maritime claims between Brunei, China, Malaysia, the Philippines, Taiwan, and Vietnam are the main source of this tension. Singapore, as a non-claimant country to the South China Sea disputes, does not take sides nor judge the merits of the rival claims. It has consistently urged "all parties to manage their differences calmly and peacefully in accordance with international law, including UNCLOS [United Nations Convention on the Law of the Sea]."1Not being a claimant does not mean that Singapore has no interest in the South China Sea. Much to the contrary, as a small state, it has an interest in ensuring that all claimant states always act in accordance with international law, including UNCLOS.2 Moreover, as an island state, Singapore has an interest in ensuring that international law preserves freedom of navigation and overflights and that such law is interpreted and applied consistently. Finally, as a Southeast Asian state, Singapore has an interest in ensuring that the Association of Southeast Asian Nations (ASEAN) remains cohesive and united and that its processes effectively advance common interests by engendering a high degree of cooperation and integration among all member states. However, little progress has been made in negotiating a binding code of conduct (C°C) in the South China Sea since the adoption of the 2002 Declaration on the Conduct of Parties in the South China Sea (D°C). Singapore, as the current country coordinator for ASEAN-China dialogue relations, hopes to make progress on that front.This essay examines Singapore's interests and role in the South China Sea in four areas: the commitment to upholding the rule of law in the relations between states, the defense of the right to freedom of navigation and overflight, the attention Singapore gives to ASEAN and the role of multilateralism in the region, and its current role as country coordinator of ASEAN-China dialogue relations.Rule of LawSingapore consistently has advocated for all parties to manage their differences calmly and peacefully in accordance with international law, including the 1982 UNCLOS. As a small country, Singapore has a fundamental interest in the peaceful settlement of international disputes in accordance with international law and its sanctioned processes rather than on the basis that might is right.3 Sovereignty disputes are governed by customary international law on the acquisition and loss of territory, not by the 1982 UNCLOS-a rather common misperception. Having presided over negotiations of the 1982 UNCLOS, Tommy Koh has iterated on various occasions that "UNCLOS contains no provisions on how to resolve sovereignty disputes over islands or other geographic features." 4 The convention does set the various maritime zones that such features could potentially generate, defines the rights and obligations in those maritime zones, and in the event that there are overlapping maritime claims, determines how the maritime boundaries can be delimited in accordance with international law. Alas, claimant states in the South China Sea have taken unilateral actions in disputed areas, such as reclaiming and building artificial islands, conducting oil and gas exploration and exploitation, and increasing military and enforcement presence, all worrying trends.At this stage, where disputes are unlikely to be resolved by negotiation, Singapore advocates reliance on rules-based regimes and mechanisms to ensure peaceful settlement of the matter. Under no circumstances should force or the threat of force be used to settle disputes among states. Practical recommendations for managing the current level of tensions include a sweeping halt to all unilateral actions contrary to international law and for claimants to clarify the extent of the various claims. …

With the growing interest among researchers, practitioners, and urban decision makers in the influence of the built environment on peoples&rsquo, health, there is increasing emphasis on using scientific knowledge to inform urban design, including methods of neuroscience. As window views are the most immediate medium of visual connection with one&rsquo, s neighbourhood, we surmised that the quality of this view would have an impact on the mental health and well-being of urban dwellers. Accordingly, we investigated how window views taken from different floors of a high-rise block with varying extents of green cover affected 29 healthy residents in an exploratory electroencephalography (EEG) experiment. The results showed that the amount of green cover within the view captured at different floor levels can cause an important interaction effect on the frontal alpha and temporal beta brain oscillations while participants view photographs. These results suggest that the brainwave patterns commonly associated with positive emotional states, motivation, and visual attention mechanisms may be increased by the extent of green cover within the view. This phenomenon seems more pronounced on the higher than lower floors. The observed findings at this stage cannot confirm major effects between floor level, green cover, and brainwaves, however, they emphasize the importance of considering the quality of window views in the planning and design of urban high-rise neighbourhoods. Having a green window view can potentially contribute to the mental health and well-being of urban dwellers.

Background Some antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. Using medical records, we compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years. Methods Patients with untreated epilepsy were indexed in the UK Clinical Practice Research Datalink and Hospital Episode Statistics database when prescribed a new EIAED or nEAAED between January 2001 and December 2010. Propensity score matching reduced confounding factors between cohorts. Patients were followed until cohort treatment failure or data cut-off. The primary outcome was the median standardized monthly direct health care cost during follow-up in 2014 £GBP, calculated using published reference costs and compared using a Mann–Whitney U test. Results The unmatched EIAED cohort (n = 2752) was older (54 vs 46 years), more likely to be male, had more comorbidities, and higher health care resource use/cost during the 1-year pre-index period (median £3014 vs £2516) than the nEAAED cohort (n = 2,137). The most common index EIAED and nEAAED were carbamazepine (63.3%) and lamotrigine (58.0%), respectively. After matching, cohorts had similar features (n = 951 each). Over up to 12 years of follow-up, the median standardized monthly direct health care cost was £229 for the EIAED and £188 for the nEAAED cohorts (p = 0.0091). The median cost was higher for the EIAED cohort in every year of follow-up. In the two cohorts, 25.1% and 20.1% of total mean cost during follow-up was epilepsy-related, with approximately 4.6% and 3.0% for AED acquisition, respectively. The median time to cohort treatment failure was shorter in the matched EIAED cohort (468 vs 1194 days). Conclusions Patients in the UK who initiated epilepsy therapy with an EIAED appeared to be at higher risk of complications associated with enzyme induction. In long-term matched cohort analyses, the median total direct health care cost associated with EIAED therapy was higher than with nEAAEDs. Changing current treatment practices could potentially improve patient outcomes and reduce costs. Electronic supplementary material The online version of this article (doi:10.1186/s12883-017-0837-y) contains supplementary material, which is available to authorized users.

A total of 1878 non-duplicate clinical Escherichia coli isolates (comprising 1711 urinary isolates and 167 blood-culture isolates), which were collected from multiple centres in Hong Kong during 1996–2008, were used to investigate the prevalence and molecular epidemiology of plasmid-mediated fosfomycin (fos) resistance genes. Eighteen of the 1878 clinical E. coli isolates were fosfomycin resistant, of which six were fosA3 positive and two were positive for another fosA variant (designated fosKP96). No isolates had the fosC2 gene. The clones of the eight isolates were diverse: sequence type (ST) 95 (n = 2), ST118 (n = 1), ST131 (n = 1), ST617 (n = 1), ST648 (n = 1), ST1488 (n = 1) and ST2847 (n = 1). In the isolates, fosA3 and bla CTX-M genes were co-harboured on conjugative plasmids with F2:A−:B− (n = 2), N (n = 1), F–:A−:B1 and N (n = 1) and untypable (n = 2) replicons. Both fosKP96-carrying plasmids belonged to replicon N. RFLP analysis showed that the two F2:A−:B− plasmids carrying fosA3 and bla CTX-M-3 genes shared the same pattern. Complete sequencing of one of the two F2:A−:B− plasmids, pFOS-HK151325 (69 768 bp) demonstrated it to be >99 % identical to the previously sequenced plasmid pHK23a originating from a pig E. coli isolate in the same region. This study demonstrated the dissemination of fosA3 genes in diverse E. coli clones on multiple bla CTX-M-carrying plasmid types, of which F2:A−:B− plasmids closely related to pHK23a were shared by isolates from human and animal sources.

Few studies have compared CTX-M encoding plasmids identified in different ecological sources. This study aimed to analyze and compare the molecular epidemiology of plasmids encoding CTX-M-14 among strains from humans and animals. The CTX-M-14 encoding plasmids in 160 Escherichia coli isolates from animal faecal (14 pigs, 16 chickens, 12 cats, 8 cattle, 5 dogs and 3 rodents), human faecal (45 adults and 20 children) and human urine (37 adults) sources in 2002-2010 were characterized by molecular methods. The replicon types of the CTX-M-14 encoding plasmids were IncFII (n=61), I1-Iγ (n=24), other F types (n=23), B/O (n=10), K (n=6), N (n=3), A/C (n=1), HI1 (n=1), HI2 (n=1) and nontypeable (n=30). The genetic environment, ISEcp1 -bla(CTX-M-14) - IS903 was found in 89.7% (52/58), 87.7% (57/65) and 86.5% (32/37) of the animal faecal, human faecal and human urine isolates, respectively. Subtyping of the 61 IncFII incompatibility group plasmids by replicon sequence typing, plasmid PCR-restriction fragment length polymorphism and marker genes (yac, malB, eitA/eitC and parB/A) profiles showed that 31% (18/58), 30.6% (20/65) and 37.8% (14/37) of the plasmids originating from animal faecal, human faecal and human urine isolates, respectively, were pHK01-like. These 52 pHK01-like plasmids originated from diverse human (20 faecal isolates from 2002, 2007 to 2008, 14 urinary isolates from 2004) and animal (all faecal, 1 cattle, 1 chicken, 5 pigs, 9 cats, 1 dog, 1 rodent from 2008 to 2010) sources. In conclusion, this study highlights the importance of the IncFII group, pHK01-like plasmids in the dissemination of CTX-M-14 among isolates from diverse sources.

To assess the occurrence of faecal carriage of Escherichia coli with resistance to 'critically important' antibiotics in various animals.Rectal or cloacal swabs were obtained weekly from cattle, pigs, chickens, cats, dogs and wild rodents over a 2 year period. Plain and antibiotic-containing medium was used for bacterial isolation. Selected isolates were characterized by molecular methods.In total, 2106 faecal specimens from 398 cats, 460 chickens, 368 dogs, 210 cattle, 214 pigs and 456 rodents were cultured. The faecal carriage rate of extended-spectrum β-lactamase (ESBL)-producing E. coli was highest in pigs (63.6%, 136/214) and lowest in rodents (4.2%, 19/456). The faecal ESBL-producing E. coli carriage rate for food-producing animals (53.6%, 474/884) was significantly higher than that for cats/dogs (14.0%, 107/766; P0.01) and wild rodents (4.2%, 19/456; P0.01). ESBL-producing isolates from food animals often (33%-81%) had multidrug (≥4) resistance to amikacin, chloramphenicol, ciprofloxacin, co-trimoxazole, gentamicin, nalidixic acid, netilmicin, nitrofurantoin and tetracycline. Most (91.2%) of the ESBL-producing isolates had CTX-M-type enzymes. A total of 10 alleles (3, 13, 14, 15, 24, 27, 28, 55, 65 and 98) from two CTX-M families (M1 and M9) were found. PFGE showed that the CTX-M-producing isolates were genetically diverse.This study shows that food animals are a major reservoir of E. coli with multidrug resistance to many antibiotics that are ranked as critically important in human medicine.

This study investigated the ability of mesenchymal stem cells (MSCs) derived from full-term human umbilical cord blood to survive, integrate and differentiate after intravitreal grafting to the degenerating neonatal rat retina following intracranial optic tract lesion. MSCs survived for 1 week in the absence of immunosuppression. When host animals were treated with cyclosporin A and dexamethasone to suppress inflammatory and immune responses, donor cells survived for at least 3 weeks, and were able to spread and cover the entire vitreal surface of the host retina. However, MSCs did not significantly integrate into or migrate through the retina. They also maintained their human antigenicity, and no indication of neural differentiation was observed in retinas where retinal ganglion cells either underwent severe degeneration or were lost. These results have provided the first in vivo evidence that MSCs derived from human umbilical cord blood can survive for a significant period of time when the host rat response is suppressed even for a short period. These results, together with the observation of a lack of neuronal differentiation and integration of MSCs after intravitreal grafting, has raised an important question as to the potential use of MSCs for neural repair through the replacement of lost neurons in the mammalian retina and central nervous system.

The aim of this study is to empirically investigate the effectiveness of The Eclectic Theory in explaining the entry mode choices of Taiwanese Electronic Components firms in China markets during the time period from 2003 to 2005. The annual data includes as many as 267, 324, and 283 firms respectively. This study explores how the ownership, location, and internalization advantages( OLI advantages) influence the entry mode choices between wholly-owned subsidiaries (WOS) and joint ventures (JV) of Taiwanese Electronic Components firms. It also identifies those factors that have an important impact on the choices of entry mode and provides meaningful suggestions for the new firms that wish to invest in the China market.

Summary Background The patterns of corticosteroids usage in severe acute respiratory syndrome (SARS) and associated treatment outcomes in Hong Kong were studied. Method Patients≥18years old who either had not received corticosteroid or had taken corticosteroids within 14days from symptom onset were included. Patients receiving corticosteroids beyond 15days or other investigational treatment within 21days from symptom onset were excluded. Of 1313 eligible patients, 1287 with major corticosteroid dosage-type combinations were analysed. Results Crude death rate was lower among 1188 steroid-treated patients compared to 99 patients in Group No Steroid (17.0% vs. 28.3%). Among four corticosteroid groups studied, mortality was lowest in the low-dose oral prednisolone (Group P) and high-dose methylprednisolone (Group MP) groups. On multivariate analysis of the corticosteroid groups, independent factors related to death were: corticosteroid group, older age, co-morbidity, worse chest X-ray score, worse respiratory status at Days 8–10 and higher admission white cell count. Again Groups P and MP had significantly lower adjusted odds ratios for death and lower bacterial and fungal culture rates. Despite worse chest X-ray scores and higher cumulative corticosteroid dosages in Group MP compared to Group P, fewer patients required rescue pulsed corticosteroid. Patients on hydrocortisone (Group HC) had the highest positive culture rates. Conclusion We speculate that corticosteroid with higher in-vitro inflammatory potency administered at timing and dosages commensurate with disease severity may be conducive to better outcome from SARS as a consequence of more effective control of immunopathological lung damage.

Neural injury due to ischemia and related insults is thought to involve the action of excitatory amino acids at N-methyl-D-aspartate receptors, which results in the influx of extracellular Ca2+ and the generation of nitric oxide. Because ethanol inhibits physiologic responses to excitatory amino acids, we examined its effect on toxicity induced by N-methyl-D-aspartate and by the nitric oxide donor sodium nitroprusside in neuron-enriched cultures prepared from rat cerebral cortex. Both N-methyl-D-aspartate and sodium nitroprusside were cytotoxic, as measured by the release of lactate dehydrogenase and by microfluorescent determination of cell viability. Ethanol (3-1,000 mM) protected cultures from N-methyl-D-aspartate but not sodium nitroprusside toxicity, and the ability of a series of n-alkanols to reproduce the effect of ethanol was related to carbon-chain length. Neuroprotection by ethanol was accompanied by a decrease in the N-methyl-D-aspartate-evoked elevation of free intracellular Ca2+ and did not appear to involve gamma-aminobutyric acid- or cyclic GMP-mediated mechanisms. These findings suggest that ethanol inhibits excitotoxicity at an early step in the N-methyl-D-aspartate signaling pathway, probably by reducing Ca2+ influx, and not by interfering with the action of nitric oxide.

The nucleus accumbens (Acb) shell and core are essential components of neural circuitry mediating the reward and motor effects produced by activation of dopamine D2 or cannabinoid-1 (CB1) receptors. D2 receptors can form heterodimeric complexes with cannabinoid-1 (CB1) receptors and are also involved in control of the availability of both dopamine and endocannabinoids. Thus, the subcellular locations of D2 and CB1 receptors with respect to each other are implicit to their physiological actions in the Acb. We used electron microscopic immunocytochemistry to determine these locations in the Acb shell and core of rat brain. In each region, many neuronal profiles showed endomembrane and plasmalemmal distributions of one or both receptors. Approximately one-third of the labeled profiles were somata and dendrites, some of which showed overlapping subcellular distributions of D2 and CB1 immunoreactivities. The remaining labeled profiles were small axons and axon terminals containing CB1 and/or D2 receptors. Of the labeled terminals forming recognizable synapses, approximately 20% of those containing CB1 receptors contacted D2-labeled dendrites, while conversely, almost 15% of those containing D2 receptors contacted CB1-labeled dendrites. These results provide the first ultrastructural evidence that D2 and CB1 receptors in the Acb shell and core have subcellular distributions supporting both intracellular associations and local involvement of D2 receptors in making available endocannabinoids that are active on CB1 receptors in synaptic neurons. These distributions have direct relevance to the rewarding and euphoric as well as motor effects produced by marijuana and by addictive drugs enhancing dopamine levels in the Acb.

The human kallikrein gene 10 (KLK10) is a member of the kallikrein gene family on chromosome 19q13.4. This gene was identified by its downregulation in breast cancer, and preliminary evidence suggests that it may act as a tumor suppressor. A computer-based analysis was performed on EST and SAGE clones from the Cancer Genome Anatomy Project and other databases. Experimental verification of differential expression of KLK10 in cancer was performed by PCR using gene-specific primers. The mRNA and EST analysis allowed the construction of the longest transcript of the gene and characterization of a 5' extension of the reported mRNA. In addition, seven new splice variants of KLK10 were identified. One of these variants, named KLK10 splice variant 3 (KLK10-SV3) which starts with a novel first exon, was experimentally verified. This variant is predicted to encode for the same protein as the 'classical' KLK10 mRNA, since the first exon is untranslated. One variant mRNA partially matches with the sequence of KLK10, while the rest of the mRNA matches with a portion of the polycystic kidney disease gene, found on chromosome 15. This variant could not be experimentally verified in either normal or cancerous tissues. There are 39 reported single nucleotide polymorphisms (SNPs) for the gene, in which three result in amino acid substitutions. SAGE analysis shows a clear upregulation of KLK10 in ovarian, pancreatic, colon, and gastric cancers. The gene is, however, downregulated in breast and prostate cancers. A three-fold decrease in expression levels was noted in actinic keratosis, compared to normal skin from the same patient. The differential regulation of KLK10 in ovarian and prostate cancers was experimentally verified by RT-PCR analysis. In addition, a significant number of clones were isolated from carcinomas of the head and neck. Fewer clones were found in carcinomas of the skin, brain and prostate. Orthologues were identified in three other species, with the highest degree of homology observed with the mouse and rat orthologues (42% in each). In conclusion new splice variants of the KLK10 gene were identified. These in silico analyses show a differential expression of the gene in various malignancies and provide the basis for directing experimental efforts to investigate the possible role of the gene as a cancer biomarker.

A 35-year-old man with a history of incomplete Reiter's syndrome presented with bilateral sequential non-arteritic ischemic optic neuropathy (NAION), which was associated with an elevated IgG titer to Chlamydia pneumoniae. Previous reports have shown that optic disc edema as part of posterior segment inflammation may be seen in patients with incomplete Reiter's syndrome. This is the first case report demonstrating NAION occurring in incomplete Reiter's syndrome. C. pneumoniae and small optic discs could have predisposed him to develop both this syndrome and NAION.

Background Information on the clinical features of the severe acute respiratory syndrome (SARS) will be of value to physicians caring for patients suspected of having this disorder. Methods We abstracted data on the clinical presentation and course of disease in 10 epidemiologically linked Chinese patients (5 men and 5 women 38 to 72 years old) in whom SARS was diagnosed between February 22, 2003, and March 22, 2003, at our hospitals in Hong Kong, China. Results Exposure between the source patient and subsequent patients ranged from minimal to that between patient and health care provider. The incubation period ranged from 2 to 11 days. All patients presented with fever (temperature, >38°C for over 24 hours), and most presented with rigor, dry cough, dyspnea, malaise, headache, and hypoxemia. Physical examination of the chest revealed crackles and percussion dullness. Lymphopenia was observed in nine patients, and most patients had mildly elevated aminotransferase levels but normal serum creatinine levels...

Part I : INTRODUCTION: SETTING THE AGENDA 1. Introduction : Naval Modernisation in Southeast Asia: Nature, Cause and Consequence, Geoffrey Till and Jane Chan 2. Naval Acquisition Trends in Asia, Bob Nugent 3. Submarines for Southeast Asia - A Major Step?, Jack McCaffrie 4. Evaluating Motivations and Performance in ASEAN Naval Acquisition Strategy, Ron Matthews and Alma Lozano 5. Towards a Theoretical Model of Weapons Acquisition: A Two-Actor `Internal Factors' Model, Adrian Kuah PART II : COMMON THEMES: COMPARATORS AND TEMPLATES 6. Comparing U.S. and Indian Naval Modernization, Richard Bitzinger 7. Naval Modernisation in China, Japan and South Korea. Contracts and Comparisons, Ian Storey PART III: SOUTHEAST ASIA CASE STUDIES 8. Vietnam: A Case Study in Naval Modernisation, Nguyen Hung Son 9. The modernisation of the Royal Malaysian Navy: challenges, trends and implications, Nizam Basiron and Lim Chee Kia 10. Philippine Naval Modernisation: Nature, Causes and Consequences, Rommel Banlaoi 11. Rebalancing Indonesia's Naval Force: Trends, Nature, and Drivers, Evan A. Laksmana 12. The Royal Thai Navy At The Beginning of The Second Decade Of The 21st Century, Wilfried A. Herrmann 13. Seeking Balance: Force Projection, Confidence-Building & the Republic of Singapore Navy, Koh Swee Lean Collin PART IV: CONSEQUENCES: NAVAL MODERNISATION AND SOUTHEAST ASIAN SECURITY 14. Regional Navies and Coast Guards: Striking a Balance between "Lawships" and Warships, Sam Bateman 15. Naval Modernisation in East Asia: Four Puzzles, Sukjoon Yoon 16. Naval Modernisation in Southeast Asia: Modernisation versus Arms Races, Bernard Loo 17. Some Tentative Conclusions, Geoffrey Till and Jane Chan