Effect of exposure energy dose on lateral resolution and flexural strength of threedimensionally printed dental zirconia

PURPOSE@#. This study aims to evaluate the effects of exposure energy on the lateral resolution and mechanical strength of dental zirconia manufactured using digital light processing (DLP). @*MATERIALS AND METHODS@#. A zirconia suspension and a custom top-down DLP printer were used for in-office manufacturing. The viscosity of the suspension and uniformity of the exposed light intensity were controlled. Based on the exposure energy dose delivered to each layer, the specimens were classified into three groups: low-energy (LE), medium-energy (ME), and high-energy (HE). For each energy group, a simplified molar cube was used to measure the widths of the outline (Xo and Yo ) and isthmus (Xi and Yi ), and a bar-shaped specimen of the sintered body was tested. A Kruskal–Wallis test for the lateral resolution and one-way analysis of variance for the mechanical strength were performed (α = .05). @*RESULTS@#. The zirconia green bodies of the ME group showed better lateral resolution than those of the LE and HE groups (both P < .001). Regarding the flexural strength of the sintered bodies, the ME group had the highest mean value, whereas the LE group had the lowest mean value (both P < .05). The ME group exhibited fewer agglomerates than the LE group, with no distinctive interlayer pores or surface defects. @*CONCLUSION@#. Based on these findings, the lateral resolution of the green body and flexural strength of the sintered body of dental zirconia could be affected by the exposure energy dose during DLP. The exposure energy should be optimized when fabricating DLPbased dental zirconia.

A review of liver fibrosis and cirrhosis regression

Cirrhosis has traditionally been considered an irreversible process of end-stage liver disease. With new treatments for chronic liver disease, there is regression of fibrosis and cirrhosis, improvement in clinical parameters (i.e. liver function and hemodynamic markers, hepatic venous pressure gradient), and survival rates, demonstrating that fibrosis and fibrolysis are a dynamic process moving in two directions. Microscopically, hepatocytes push into thinning fibrous septa with eventual perforation leaving behind delicate periportal spikes in the portal tracts and loss of portal veins. Obliterated portal veins during progressive fibrosis and cirrhosis due to parenchymal extinction, vascular remodeling and thrombosis often leave behind a bile duct and hepatic artery within the portal tract. Traditional staging classification systems focused on a linear, progressive process; however, the Beijing classification system incorporates both the bidirectional nature for the progression and regression of fibrosis. However, even with regression, vascular lesions/remodeling, parenchymal extinction and a cumulative mutational burden place patients at an increased risk for developing hepatocellular carcinoma and should continue to undergo active clinical surveillance. It is more appropriate to consider cirrhosis as another stage in the evolution of chronic liver disease as a bidirectional process rather than an end-stage, irreversible state.

Differentially Expressed mRNA in Streptozotocin-Induced Diabetic Bladder Using RNA Sequencing Analysis / 대한배뇨장애요실금학회지

Purpose@#To detect elements governing the pathogenesis of diabetic cystopathy (DC), mRNA sequencing was carried out for bladder tissues from normal rats and those with induced diabetes mellitus (DM). This research therefore offers possible underlying molecular pathways for the advancement of DC in relation to differential mRNA expression, together with visceral functional and architectural alterations noted in individuals with this condition. @*Methods@#An intraperitoneal injection of streptozotocin (STZ) was utilized to provoke DM in male Sprague-Dawley rats. Dysregulation and significant variations between normal rats and those with induced DM were then identified by a fold change of ≥ 1.5 with a false discovery rate P < 0.05. Hierarchical clustering/heat map and Gene Ontology/DAVID reference sources were generated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction analysis were then performed. @*Results@#The diabetic rodent group exhibited a greater residual urine volume (4.0 ± 0.4 mL) than their control counterparts (0.7 ± 0.2 mL, P < 0.01) at 12 weeks after diagnosis of diabetes. Expression analysis revealed 16 upregulated and 4 downregulated genes in STZDM bladder samples. A notable increase in expression was seen in PTHLH, TNFAIP6, PRC1, MAPK10, LOC686120, CASQ2, ACTG2, PDLIM3, FCHSD1, DBN1, NKD2, PDLIM7, ATF4, RBPMS2, ITGB1 and HSPB8. A notable decrease in expression was seen in SREBLF1, PBGFR1, PBLD1 and CELF1. Major genetic themes associated with mRNA upregulation and downregulation ware identified via Gene Ontology analysis and KEGG pathways. Protein to protein interaction analysis detected PDLIM3, PDLIM7, ITGB1, ACTG2 as core high frequency nodes within the network. @*Conclusions@#Changes in mRNA expression together with biological process and pathways that contribute to the etiologies underlying visceral impairment of the bladder in DM are evident. Our strategy is promising for recognizing mRNAs exclusive to the bladder in DM that might offer useful targets for diagnosis and treatment.

A Critical Involvement of Glutamatergic Neurons in the Anterior Insular Cortex for Subdiaphragmatic Vagotomy-induced Analgesia

Subdiaphragmatic vagotomy (SDV) is known to produce analgesic effect in various pain conditions including not only visceral pain but also somatic pain. We aimed to determine brain mechanisms by which SDV induces analgesic effect in somatic pain condition by using formalin-induced acute inflammatory pain model. We identified brain regions that mediate SDV-induced analgesic effect on acute inflammatory pain by analyzing cFos expression in the whole brain. We found that c-Fos expression was specifically increased in the anterior insular cortex (aIC) among subregions of the insular cortex in acute inflammatory pain, which was reversed by SDV. These results were not mimicked in female mice, indicating sexualdimorphism in SDV-induced analgesia. SDV decreased c-Fos expressions more preferentially in glutamatergic neurons rather than GABAergic neurons in the aIC, and pharmacological activation of glutamatergic neurons with NMDA in the aIC inhibited SDV-induced analgesic effect. Furthermore, chemogenetic activation of glutamatergic neurons in the aIC reversed SDV-induced analgesia. Taken together, our results suggest that the decrease in the neuronal activity of glutamatergic neurons in the aIC mediates SDV-induced analgesic effect, potentially serving as an important therapeutic target to treat inflammatory pain.

Contemporary Unplanned Readmission Trends Following Management of Type B Aortic Dissection

Purpose@#Large studies have demonstrated improved survival outcomes with thoracic endovascular aortic repair (TEVAR) at two and five years compared to medical therapy; however, early TEVAR for acute type B aortic dissection (TBAD) remains controversial. We aimed to evaluate trends and clinical predictors of hospital readmissions in patients undergoing medical management and TEVAR for acute TBADs. @*Materials and Methods@#The Nationwide Readmissions Database was queried for all 30-day and 90-day index readmissions (30D-IR and 90D-IR, respectively) after a diagnosis of a TBAD from January 2012 to September 2015. Data on readmission diagnosis, patient demographics, and hospital characteristics were collected from readmitted patients and analyzed. Multivariable logistic regression models were used to identify the predictors of readmission after TEVAR or medical medical management of TBAD. @*Results@#We identified 53,117 patients with acute TBAD. Medical management was the initial treatment modality in 46,985 (88.4%) patients, while 6,132 (11.5%) underwent TEVAR. Factors including older patient age, lower household income, severity of comorbidities, initial hospital length of stay, and urgent procedure demonstrated an increased likelihood of experiencing 30D-IR and 90D-IR (P<0.05).The rate of unplanned readmission for patients undergoing medical management remained stable (11.3% vs. 10.0% for 30D-IR; 19.1% vs. 15.5% for 90D-IR). Reasons for unplanned readmission in the TEVAR cohort were largely related to technical complications. There was no significant difference in readmission costs between medical management and TEVAR. @*Conclusion@#Number of unplanned readmissions in the TEVAR arm decreased significantly over time, whereas the number of readmissions for medical management remained stable.

Patterns of Restricted and Repetitive Behaviors in Toddlers and Young Children with Autism Spectrum Disorder

Objectives@#Restricted and repetitive behaviors (RRBs) are a core symptom in the diagnosis of autism spectrum disorder (ASD). The complexity of behavioral patterns has called for the creation of phenotypically homogeneous subgroups among individuals with ASD.The purpose of this study was 1) to investigate the different types of RRBs and 2) to explore whether subgroups created by RRBs would show unique levels of functioning in toddlers and young children with ASD. @*Methods@#A total of 313 children with ASD, aged 12–42 months were included in the analysis. The Autism Diagnostic Interview-Revised was used to obtain information on the different types of RRBs by grouping 15 items into six categories. The Vineland Adaptive Behaviors Scale, a parent-reported questionnaire, was used to measure adaptive functioning. A portion of the children were analyzed separately for verbal-related RRBs based on their expressive language level. Two-step cluster analysis using RRB groups as features was used to create subgroups. Analysis of covariance while covarying for age and language was performed to explore the clinical characteristics of each cluster group. @*Results@#Sensory-related RRBs were the most prevalent, followed by circumscribed interests, interest in objects, resistance to change, and repetitive body movements. A subset of the children was analyzed separately to explore verbal-related RRBs. Four cluster groups were created based on reported RRBs, with multiple RRBs demonstrating significant delays in adaptive functioning. @*Conclusion@#Heterogeneity of RRBs emerges at a young age. The different patterns of RRBs can be used as valuable information to determine developmental trajectories with better implications for treatment approaches.

Enhanced Hypoxia-Associated Genes in Impaired Contractility From Bladder Outlet Obstruction

Background@#Hypoxia damages the bladder wall and contributes to the initiation of bladder dysfunction. The change of hypoxia is not well known in impaired bladder contractility caused by long-term bladder outlet obstruction (BOO). We aimed to find out whether hypoxia of bladder tissue is present and what signaling mechanisms are involved in the decompensated bladder in BOO. @*Methods@#Twenty 6-week-old female Sprague-Dawley rats were divided into 2 groups, 10 rats each: group 1, sham operation; group 2, BOO for 8 weeks. Eight weeks after the onset of BOO, we did cystometric evaluation and processed polymerase chain reaction (PCR) array for hypoxia pathway using bladder tissues. The PCR array consists of 84 genes known to be involved in the hypoxic response, cell differentiation, and metabolism. We did quantitative PCR (qPCR) and immunohistochemical staining of bladder tissue for hypoxia. @*Results@#Eight genes were at least 2-fold upregulated and 3 genes were at least 2-fold downregulated in BOO group, compared with the sham operation group. The up-regulated genes (fold change) belonging to the hypoxia-inducible factor (HIF) 1 interactor included Cdkn2a (11.0), and the down-regulated genes belonging to HIF and co-transcription factors included Hif3a (−39.6) and Per1 (−5.1) by BOO. Genes influenced each other by means of TGFβ1, TNF, and TP53. @*Conclusion@#Hypoxia genes were increased in impaired contractility because of long-term BOO. The gene expression profiles could explain the molecular mechanisms of hypoxia in impaired contractility because of long-term BOO.

Factors influencing protective behaviours during haze episodes in Singapore: A population-based study

INTRODUCTION@#Haze is a recurrent problem in Southeast Asia. Exposure to haze is linked to ophthalmic, respiratory and cardiovascular diseases, and mortality. In this study, we investigated the role of demographic factors, knowledge and perceived risk in influencing protective behaviours during the 2013 haze in Singapore.@*METHODS@#We evaluated 696 adults in a cross-sectional study. Participants were sampled via a 2-stage simple random sampling without replacement from a large residential district in Singapore in 2015. The questionnaire measured the participant's knowledge, perceived risk and behaviours during the Southeast Asian haze crisis in 2013. Reliability and validity of the questionnaire were assessed using comparative fit index (≥0.96) and root mean square error of approximation (≤0.05). We performed structural equation modelling to examine the relationship between the hypothesised factors and protective behaviours.@*RESULTS@#More than 95% of the individuals engaged in at least 1 form of protective behaviour. Knowledge was strongly associated with protective behaviours via direct effect (β=0.45, 95% CI 0.19-0.69, @*CONCLUSION@#Knowledge was associated with protective behaviours, suggesting the importance of public education. Efforts should target those of lower education level and smokers. The wearing of N95 masks correlates with uptake of other protective behaviours.

Functional annotation of lung cancer‒associated genetic variants by cell type‒specific epigenome and long-range chromatin interactome

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer‒associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type‒specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer‒associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.

Functional annotation of lung cancer‒associated genetic variants by cell type‒specific epigenome and long-range chromatin interactome

Functional interpretation of noncoding genetic variants associated with complex human diseases and traits remains a challenge. In an effort to enhance our understanding of common germline variants associated with lung cancer, we categorize regulatory elements based on eight major cell types of human lung tissue. Our results show that 21.68% of lung cancer‒associated risk variants are linked to noncoding regulatory elements, nearly half of which are cell type‒specific. Integrative analysis of high-resolution long-range chromatin interactome maps and single-cell RNA-sequencing data of lung tumors uncovers number of putative target genes of these variants and functionally relevant cell types, which display a potential biological link to cancer susceptibility. The present study greatly expands the scope of functional annotation of lung cancer‒associated genetic risk factors and dictates probable cell types involved in lung carcinogenesis.

Platinum complexes of curcumin delivered by dual-responsive polymeric nanoparticles improve chemotherapeutic efficacy based on the enhanced anti-metastasis activity and reduce side effects

Platinum-based chemotherapy is used for non-small cell lung cancer (NSCLC). However, it has side effects and minimum efficacy against lung cancer metastasis. In this study, platinum-curcumin complexes were loaded into pH and redox dual-responsive nanoparticles (denoted as Pt-CUR@PSPPN) to facilitate intracellular release and synergistic anti-cancer effects. Pt-CUR@PSPPN was prepared by a nano-precipitation method and had a diameter of ∼100 nm. The nanoparticles showed increased anti-cancer effects both and . In addition, Pt-CUR@PSPPN blocked PI3K/AKT signal transduction pathway and inhibited MMP2 and VEGFR2, resulting in enhanced anti-metastatic activity. Furthermore, reduced side effects were also observed. In conclusion, Pt-CUR@PSPPN provided a novel and attractive therapeutic strategy for NSCLC.

Ex Vivo T Cell Cytokine Expression Predicts Survival in Patients with Severe Alcoholic Hepatitis

Alcoholic hepatitis (AH) is an acute inflammatory liver condition with high early mortality rate. Steroids improve shortterm survival but nonresponders have the worst outcomes.There is a clinical need to identify these high-risk individuals at the time of presentation. T cells are implicated in AH and steroid responsiveness. We measured ex vivo T cell cytokine expression as a candidate biomarker of outcomes in patients with AH. Consecutive patients (bilirubin >80 µmol/L and ratio of aspartate aminotransferase to alanine aminotransferase >1.5 who were heavy alcohol consumers with discriminant function [DF] ≥32), were recruited from University Hospitals Plymouth NHS Trust. T cells were obtained and stimulated ex vivo. Cytokine expression levels were determined by flow cytometry and protein multiplex analysis. Twenty-three patients were recruited (10 male; median age 51 years; baseline DF 67; 30% 90-day mortality). Compared to T cells from nonsur-vivors at day 90, T cells from survivors had higher baseline baseline intracellular interleukin (IL)-10:IL-17A ratio (0.43 vs 1.20, p=0.02). Multiplex protein analysis identified interferon γ (IFNγ) and tumor necrosis factor-α (TNF-α) as independent predictors of 90-day mortality (p=0.04, p=0.01, respectively).The ratio of IFNγ to TNF-α was predictive of 90-day mortality (1.4 vs 0.2, p=0.03). These data demonstrate the potential utility of T cell cytokine release assays performed on pretreatment blood samples as biomarkers of survival in patients with severe AH. Our key findings were that intracellular IL-10:IL-17A and IFNγ:TNF-α in culture supernatants were pre-dictors of 90-day mortality. This offers the promise of devel-oping T cell-based diagnostic tools for risk stratification.

Hypocrellin A-based photodynamic action induces apoptosis in A549 cells through ROS-mediated mitochondrial signaling pathway

Over recent decades, many studies have reported that hypocrellin A (HA) can eliminate cancer cells with proper irradiation in several cancer cell lines. However, the precise molecular mechanism underlying its anticancer effect has not been fully defined. HA-mediated cytotoxicity and apoptosis in human lung adenocarcinoma A549 cells were evaluated after photodynamic therapy (PDT). A temporal quantitative proteomics approach by isobaric tag for relative and absolute quantitation (iTRAQ) 2D liquid chromatography with tandem mass spectrometric (LC-MS/MS) was introduced to help clarify molecular cytotoxic mechanisms and identify candidate targets of HA-induced apoptotic cell death. Specific caspase inhibitors were used to further elucidate the molecular pathway underlying apoptosis in PDT-treated A549 cells. Finally, down-stream apoptosis-related protein was evaluated. Apoptosis induced by HA was associated with cell shrinkage, externalization of cell membrane phosphatidylserine, DNA fragmentation, and mitochondrial disruption, which were preceded by increased intracellular reactive oxygen species (ROS) generations. Further studies showed that PDT treatment with 0.08 µmol/L HA resulted in mitochondrial disruption, pronounced release of cytochrome , and activation of caspase-3, -9, and -7. Together, HA may be a possible therapeutic agent directed toward mitochondria and a promising photodynamic anticancer candidate for further evaluation.

Comfort and exertion while using filtering facepiece respirators with exhalation valve and an active venting system among male military personnel

<p><b>INTRODUCTION</b>This study aimed to determine if disposable filtering facepiece respirators (FFRs) that come with an exhalation valve (EV) and a novel active venting system (AVS) provided greater perceived comfort and exertion when compared to standard N95 FFRs without these features among male military personnel performing prolonged essential outdoor duties.</p><p><b>METHODS</b>We used a randomised open-label controlled crossover study design to compare three FFR options: (a) standard FFR; (b) FFR with EV; and (c) FFR with EV+AVS. Male military personnel aged between 18 and 20 years completed a questionnaire at the start of outdoor duty (baseline), after two hours of standardised non-strenuous outdoor duty and after 12 hours of duty divided into two-hour work-rest cycles. Participants rated the degree of discomfort, exertion and symptoms using a five-point Likert scale. The association between outcomes and types of FFR was assessed using a multivariate ordered probit mixed-effects model.</p><p><b>RESULTS</b>For a majority of the symptoms, study participants gave FFR with EV and FFR EV+AVS significantly better scores than standard FFR. Both FFR with EV and FFR with EV+AVS had significantly less discomfort (FFR with EV+AVS: 91.1%; FFR with EV: 57.6%) and exertion (FFR with EV+AVS: 83.5%; FFR with EV: 34.4%) than standard FFR. FFR with EV+AVS also had significantly better scores for exertion (53.4%) and comfort (39.4%) when compared to FFR with EV.</p><p><b>CONCLUSION</b>Usage of FFR with EV+AVS resulted in significantly reduced symptoms, discomfort and exertion when compared to FFR with EV and standard FFR.</p>

possibility of hormone-mediated PSA derangement in prostate cancer treatment

Background: this study was designed to suggest the possibility of hormone-related derangement in salvage radiotherapy [SRT] after radical prostatectomy in terms of prostate-specific antigen [PSA] control

Materials and Methods: among 160 consecutive prostate cancer patients who received radical prostatectomy, 34 with SRT between 2004 and 2012 were retrospectively reviewed. The numbers of patients with pathologic T3-T4 stage, Gleason score 8-10, and positive resection margin were 11 [32.4%], 10 [29.4%], and 17 [50.0%], respectively. Median SRT dose was 64.8 Gy [range, 52.9-70.0 Gy] with 1.8-2.3 Gy fractionations. Biochemical failure -free survival after SRT was counted and the median follow-up period was 32.5 months [range, 10-118 months]

Results: after SRT, the median _me for PSA to decrease to less than 0.2 ng/mL was four months [range, 0-25 months]. The three-year survival rate was 60.3%. On univariate analysis, preferential hormone therapy [PHT] [p=0.022], higher PSA at SRT [p=0.005], and higher PSA after surgery [p=0.003] were related to a shorter biochemical survival period. On multivariate analysis, lower PSA at SRT [p=0.016], higher radiation dose [p=0.007], and non-PHT [p=0.046] suggested a consistent PSA control

Conclusion: according to these results, low PSA values by hormonal intervention need to be reconsidered with a different way to look at the relationship between the PSA and hormone therapy. SRT should be considered for postoperative salvage treatment regardless of the hormone-related PSA values

Effect of coenzyme Qio on radiation-induced fatigue in rats

Background: Fatigue is a common side effect in cancer patients undergoing radiation therapy [RT]. Radiation-induced fatigue affects the quality of life, but there is no definitive treatment option, in this study, the weight-loaded forced swim test was performed to assess the effect of coenzyme QIO [CoQIO] on radiation-induced fatigue

Materials and Methods: A total of 60 rats were divided randomly and equally into four groups: No swim, No RT, RT + placebo, or RT + CoQIO. The No swim, No RT, and RT + placebo groups received 1 ml of soybean oil daily for 14 days. The RT + CoQIO group received 100 mg/kg of CoQIO in soybean oil at the same times. Both RT groups were irradiated with 10 Gy on the 14th day of treatment. The swim test with sinkers weighing 10% of body weight was performed 24 h later in all animals except the No swim group

Results: The level of blood urea nitrogen [BUN] was significantly lower in the No swim than the other groups. The BUN level of the No RT group was significantly decreased compared with the RT + placebo group, but it did not differ from the RT + CoQIO group. Swimming times to complete exhaustion were significantly longer in the No RT and RT + CoQIO groups compared to the RT + placebo group [99.4, 105.9, and 75.7 s, respectively] [P<0.001]

Conclusion: Supplementation with CoQIO can prevent the decrease in endurance capacity caused by radiation

Dosimetric accuracy of the Acuros XB and Anisotropic analytical algorithm near interface of the different density media for the small fields of a 6- MV flattening-filter-free beam

Background: This study was conducted to assess the accuracy of dose calculation near the air-phantom interface of a heterogeneous phantom for Acuros XB [AXB] and Anisotropic Analytical Algorithm [AAA] algorithm of a 6-MV flattening-filter-free beam, compared with film measurements

Materials and Methods: A phantom included air gap was specially manufactured for this study. In order to evaluate the dose near air gap-phantom interface, Eclipse treatment planning system equipped both AXB and AAA was used for the dose calculations. Measurements in this region were performed with radiochromic film. The central-axis dose [CAD] and off-axis dose [OAD] between calculations and measurements were analyzed for various field sizes and air gaps. The root-mean-square-error [RMSE] was used to evaluate the difference between the calculated and measured OAD. In order to quantify agreement between the calculated and measured dose distributions, the gamma analysis was performed with the 2%/2 mm and 3%/3 mm criteria

Results: For all fields traveling through 1 and 3 cm air gap, the maximum difference in the calculated CAD was -5.3% for AXB and 214.8% for AAA, compared to the measured CAD. For the RMSE between the calculated and measured OAD, the calculated OAD using AXB showed interval in the RMSE [from 4.4 to 12.7] while using AAA indicated broad [from 7.7 to 101.0]. In addition, the gamma passing rates showed that AXB was higher agreement than AAA

Conclusion: This study demonstrated that AXB was more accurate in heterogeneous media near air-phantom interface than AAA when comparing the measured data

Historic accounts of Mansonella parasitaemias in the South Pacific and their relevance to lymphatic filariasis elimination efforts today

There are two species of filarial parasites with sheathless microfilariae known to commonly cause parasitaemias in humans: Mansonella perstans and Mansonella ozzardi. In most contemporary accounts of the distribution of these parasites, neither is usually considered to occur anywhere in the Eastern Hemisphere. However, Sir Patrick Manson, who first described both parasite species, recorded the existence of sheathless sharp-tailed Mansonella ozzardi-like parasites occurring in the blood of natives from New Guinea in each and every version of his manual for tropical disease that he wrote before his death in 1922. Manson's reports were based on his own identifications and were made from at least two independent blood sample collections that were taken from the island. Pacific region Mansonella perstans parasitaemias were also later (in 1923) reported to occur in New Guinea and once before this (in 1905) in Fiji. Although Mansonella-parasitaemias are generally regarded as benign, they are thought to be of public health importance because they can affect the epidemiological monitoring of other filarial diseases. In this article, we reviewed the historic literature concerning Pacific-origin Mansonella-parasitaemias in an attempt to explain how, despite repeated reports of Pacific-region Mansonella-parasitaemias, by as early as the 1970s, the WHO had arrived at the present-day view that Wuchereria bancrofti is the only cause of filarial parasitaemias in Papua New Guinea. We have also evaluated the evidence supporting the contemporary existence of Pacific-area parasitaemia-causing Mansonella parasites and assessed the relevance such parasites could have for present-day lymphatic filariasis elimination efforts in the region.

T-cell-mediated drug hypersensitivity: immune mechanisms and their clinical relevance

T-cell-mediated drug hypersensitivity represents a significant proportion of immune mediated drug hypersensitivity reactions. In the recent years, there has been an increase in understanding the immune mechanisms behind T-cell-mediated drug hypersensitivity. According to hapten mechanism, drug specific T-cell response is stimulated by drug-protein conjugate presented on major histocompatibility complex (MHC) as it is presented as a new antigenic determinant. On the other hand, p-i concept suggests that a drug can stimulate T cells via noncovalent direct interaction with T-cell receptor and/or peptide-MHC. The drug binding site is quite variable and this leads to several different mechanisms within p-i concept. Altered peptide repertoire can be regarded as an 'atypical' subset of p-i concept since the mode of the drug binding and the binding site are essentially identical to p-i concept. However, the intracellular binding of abacavir to HLA-B*57:01 additionally results in alteration in peptide repertoire. Furthermore the T-cell response to altered peptide repertoire model is only shown for abacavir and HLA-B*57:01 and therefore it may not be generalised to other drug hypersensitivity. Danger hypothesis has been postulated to play an important role in drug hypersensitivity by providing signal 2 but its experimental data is lacking at this point in time. Furthermore, the recently described allo-immune response suggests that danger signal may be unnecessary. Finally, in view of these new understanding, the classification and the definition of type B adverse drug reaction should be revised.

Reduced Mortality by Physician-Staffed HEMS Dispatch for Adult Blunt Trauma Patients in Korea

The aim of this study was to investigate the efficiency of domestic physician-staffed helicopter emergency medical service (HEMS) for the transport of patients with severe trauma to a hospital. The study included patients with blunt trauma who were transported to our hospital by physician-staffed HEMS (Group P; n = 100) or nonphysician-staffed HEMS (Group NP; n = 80). Basic patient characteristics, transport time, treatment procedures, and medical treatment outcomes assessed using the Trauma and Injury Severity Score (TRISS) were compared between groups. We also assessed patients who were transported to the hospital within 3 h of injury in Groups P (Group P3; n = 50) and NP (Group NP3; n = 74). The severity of injury was higher, transport time was longer, and time from hospital arrival to operation room transfer was shorter for Group P than for Group NP (P < 0.001). Although Group P patients exhibited better medical treatment outcomes compared with Group NP, the difference was not statistically significant (P = 0.134 vs. 0.730). However, the difference in outcomes was statistically significant between Groups P3 and NP3 (P = 0.035 vs. 0.546). Under the current domestic trauma patient transport system in South Korea, physician-staffed HEMS are expected to increase the survival of patients with severe trauma. In particular, better treatment outcomes are expected if dedicated trauma resuscitation teams actively intervene in the medical treatment process from the transport stage and if patients are transported to a hospital to receive definitive care within 3 hours of injury.