Measuring the effects of typhoon trajectories on dengue outbreaks in tropical regions of Taiwan: 1998-2019.

Dengue fever is a rapidly spreading mosquito-borne contagion. However, the effects of extreme rainfall events on dengue occurrences have not been widely evaluated. With their immense precipitation and high winds, typhoons may have distinct effects on dengue occurrence from those during other heavy rain events. Frequented by typhoons and situated in the tropical climate zone, southern Taiwan is an appropriate study area due to its isolated geographic environment. Each subject to distinct orographic effects on typhoon structure and typhoon-induced precipitation, 9 typhoon trajectories around Taiwan have not been observed until now. This study analyzes typhoon-induced precipitation and examines historical typhoon events by trajectory to determine the effects of typhoons on dengue occurrences in different urban contexts of Tainan and Kaohsiung in high-epidemic southern Taiwan. We employed data from 1998 to 2019 and developed logistic regression models for modeling dengue occurrence while taking 28-day lag effects into account. We considered factors including typhoon trajectory, occurrence, and typhoon-induced precipitation to dengue occurrences. Our results indicate that typhoon trajectories are a significant risk factor for dengue occurrence. Typhoons affect dengue occurrence differently by trajectory. One out of four northbound (along the Taiwan Strait) and four out of five westbound (across Taiwan) typhoons were found to be positively correlated with dengue occurrences in southern Taiwan. We observe that typhoon-induced precipitation is not associated with dengue occurrence in southern Taiwan, which suggests that wind destruction during typhoon events may serve as the primary cause for their positive effects by leaving debris suitable for mosquito habitats. Our findings provide insights into the impact of typhoons by trajectory on dengue occurrence, which can improve the accuracy of future dengue forecasts in neighboring regions with similar climatic contexts.

State-of-the-Art Capability of Convolutional Neural Networks to Distinguish the Signal in the Ionosphere.

Recovering and distinguishing different ionospheric layers and signals usually requires slow and complicated procedures. In this work, we construct and train five convolutional neural network (CNN) models: DeepLab, fully convolutional DenseNet24 (FC-DenseNet24), deep watershed transform (DWT), Mask R-CNN, and spatial attention-UNet (SA-UNet) for the recovery of ionograms. The performance of the models is evaluated by intersection over union (IoU). We collect and manually label 6131 ionograms, which are acquired from a low-latitude ionosonde in Taiwan. These ionograms are contaminated by strong quasi-static noise, with an average signal-to-noise ratio (SNR) equal to 1.4. Applying the five models to these noisy ionograms, we show that the models can recover useful signals with IoU > 0.6. The highest accuracy is achieved by SA-UNet. For signals with less than 15% of samples in the data set, they can be recovered by Mask R-CNN to some degree (IoU > 0.2). In addition to the number of samples, we identify and examine the effects of three factors: (1) SNR, (2) shape of signal, (3) overlapping of signals on the recovery accuracy of different models. Our results indicate that FC-DenseNet24, DWT, Mask R-CNN and SA-UNet are capable of identifying signals from very noisy ionograms (SNR < 1.4), overlapping signals can be well identified by DWT, Mask R-CNN and SA-UNet, and that more elongated signals are better identified by all models.

Recovery of Ionospheric Signals Using Fully Convolutional DenseNet and Its Challenges.

The technique of active ionospheric sounding by ionosondes requires sophisticated methods for the recovery of experimental data on ionograms. In this work, we applied an advanced algorithm of deep learning for the identification and classification of signals from different ionospheric layers. We collected a dataset of 6131 manually labeled ionograms acquired from low-latitude ionosondes in Taiwan. In the ionograms, we distinguished 11 different classes of the signals according to their ionospheric layers. We developed an artificial neural network, FC-DenseNet24, based on the FC-DenseNet convolutional neural network. We also developed a double-filtering algorithm to reduce incorrectly classified signals. That made it possible to successfully recover the sporadic E layer and the F2 layer from highly noise-contaminated ionograms whose mean signal-to-noise ratio was low, SNR = 1.43. The Intersection over Union (IoU) of the recovery of these two signal classes was greater than 0.6, which was higher than the previous models reported. We also identified three factors that can lower the recovery accuracy: (1) smaller statistics of samples; (2) mixing and overlapping of different signals; (3) the compact shape of signals.

The Mandible Ameliorates Facial Allograft Rejection and Is Associated with the Development of Regulatory T Cells and Mixed Chimerism.

Vascularized composite allografts contain various tissue components and possess relative antigenicity, eliciting different degrees of alloimmune responses. To investigate the strategies for achieving facial allograft tolerance, we established a mouse hemiface transplant model, including the skin, muscle, mandible, mucosa, and vessels. However, the immunomodulatory effects of the mandible on facial allografts remain unclear. To understand the effects of the mandible on facial allograft survival, we compared the diversities of different facial allograft-elicited alloimmunity between a facial osteomyocutaneous allograft (OMC), including skin, muscle, oral mucosa, and vessels, and especially the mandible, and a myocutaneous allograft (MC) including the skin, muscle, oral mucosa, and vessels, but not the mandible. The different facial allografts of a BALB/c donor were transplanted into a heterotopic neck defect on fully major histocompatibility complex-mismatched C57BL/6 mice. The allogeneic OMC (Allo-OMC) group exhibited significant prolongation of facial allograft survival compared to the allogeneic MC group, both in the presence and absence of FK506 immunosuppressive drugs. With the use of FK506 monotherapy (2 mg/kg) for 21 days, the allo-OMC group, including the mandible, showed prolongation of facial allograft survival of up to 65 days, whereas the myocutaneous allograft, without the mandible, only survived for 34 days. The Allo-OMC group also displayed decreased lymphocyte infiltration into the facial allograft. Both groups showed similar percentages of B cells, T cells, natural killer cells, macrophages, and dendritic cells in the blood, spleen, and lymph nodes. However, a decrease in pro-inflammatory T helper 1 cells and an increase in anti-inflammatory regulatory T cells were observed in the blood and lymph nodes of the Allo-OMC group. Significantly increased percentages of donor immune cells were also observed in three lymphoid organs of the Allo-OMC group, suggesting mixed chimerism induction. These results indicated that the mandible has the potential to induce anti-inflammatory effects and mixed chimerism for prolonging facial allograft survival. The immunomodulatory understanding of the mandible could contribute to reducing the use of immunosuppressive regimens in clinical face allotransplantation including the mandible.

Increased GABAergic inhibitory function against ischemic long-term potentiation in the CA1 region of the hippocampus.

Potentiation of N-methyl-D-aspartate receptor (NMDAR)-mediated excitatory synaptic plasticity around 1 h after brief exposure to anoxia/aglycemia is called ischemic long-term potentiation (iLTP), which is considered a pathological form of synaptic response during the early phase of ischemic stroke. It is known that GABAergic inhibitory transmission is also an important molecular process involved in synaptic plasticity and learning memory. However, whether GABAergic transmission is involved in iLTP and early-phase plasticity in ischemic stroke remains unknown. In this study, iLTP was found to be induced in the hippocampal Schaffer-collateral pathway by exposure to oxygen glucose deprivation (OGD). Western blot analysis was conducted to analyze excitatory synaptic receptors and inhibitory synaptic receptors following OGD. The ß3 subunit of the GABAA receptor (GABAAR) was markedly reduced, whereas the GluN2B subunit of the NMDAR was increased in the hippocampal area in the OGD group. Using extracellular recording, we demonstrated that application of GABAAR agonist midazolam could abolish the hippocampal iLTP. Moreover, midazolam had no significant effect on the increase in NMDAR subunit GluN2B, but ameliorated the reduction in the ß3 subunit of GABAAR after OGD. In summary, our results indicated that hippocampal GABAAR reduction promoted synaptic potentiation after OGD. Activation of GABAergic inhibitory transmission function could inhibit iLTP; thus, modulation of GABAergic function is a protective treatment method in the acute phase of synaptic plasticity in ischemic stroke.

Low-Valent, Multiply Bonded, Trigonal-Planar Sb Complex: Rational Syntheses, Dual Acidic/Basic Properties, and Unexpected Semiconducting Characteristics.

A 4-center, 6π-conjugated, multiply bonded trigonal-planar complex, [Sb{Cr(CO)5}3]- (1), was synthesized via the hydride abstraction of [HSb{Cr(CO)5}3]2- (1-H) with HBF4·H2O, with the release of high yields of H2. The oxidation state of the Sb atom in [Et4N][1] was well-defined as 0, which was evidenced by X-ray photoelectron spectroscopy and X-ray absorption near-edge structure. The distinct color-structure relationship of this low-valent Sb complex 1 toward a wide range of organic solvents was demonstrated, as interpreted by time-dependent density functional theory calculations, allowing the trigonal-planar 1 and the tetrahedral solvent adducts to be probed, revealing the dual acid/base properties of the Sb center. In addition, 1 showed pronounced electrophilicity toward anionic and neutral nucleophiles, even with solvent molecules, to produce tetrahedral complexes [(Nu)Sb{Cr(CO)5}3]n- [1-Nu; n = 2, Nu = H, F, Cl, Br, I, OH; n = 1, Nu = PEt3, PPh3, N,N-dimethylformamide (DMF), acetonitrile (MeCN)]. On the contrary, the Fe/Cr hydride complex [HSb{Fe(CO)4}{Cr(CO)5}2]2- (2-H) was obtained by treating 1 with [HFe(CO)4]-. Upon hydride abstraction of 2-H with HBF4·H2O or [CPh3][BF4], a multiply bonded Fe/Cr trigonal-planar complex, [Sb{Fe(CO)4}{Cr(CO)5}2]- (2), was produced in which the oxidation coupling Sb2-containing complexes [Sb2Cr4Fe2(CO)28]2- (3-Cr) and [HSb2Cr3Fe2(CO)23]- (3-H) were yielded as final products. Complex 3-Cr exhibited dual Lewis acid/base properties via hydridation and protonation reactions, to form 2-H or 3-H, respectively. Surprisingly, [Et4N][1] possessed a low energy gap of 1.13 eV with an electrical conductivity in the range of (1.10-2.77) × 10-6 S·cm-1, showing that [Et4N][1] was a low-energy-gap semiconductor. The crystal packing, crystal indexing, and density of states results of [Et4N][1] further confirmed the efficient through-space conduction pathway via the intermolecular Sb···O(carbonyl) and O(carbonyl)···O(carbonyl) interactions of the 1D anionic zigzag chain of 1.

Human Wharton's Jelly Mesenchymal Stem Cell-Mediated Sciatic Nerve Recovery Is Associated with the Upregulation of Regulatory T Cells.

The acceleration of peripheral nerve regeneration is crucial for functional nerve recovery. Our previous study demonstrated that human Wharton's jelly-derived mesenchymal stem cells (hWJ-MSC) promote sciatic nerve recovery and regeneration via the direct upregulation and release of neurotrophic factors. However, the immunomodulatory role of hWJ-MSC in sciatic nerve recovery remains unclear. The effects of hWJ-MSC on innate immunity, represented by macrophages, natural killer cells, and dendritic cells, as well as on adaptive immunity, represented by CD4+ T, CD8+ T, B, and regulatory T cells (Tregs), were examined using flow cytometry. Interestingly, a significantly increased level of Tregs was detected in blood, lymph nodes (LNs), and nerve-infiltrating cells on POD7, 15, 21, and 35. Anti-inflammatory cytokines, such as IL-4 and IL-10, were significantly upregulated in the LNs and nerves of hWJ-MSC-treated mice. Treg depletion neutralized the improved effects of hWJ-MSC on sciatic nerve recovery. In contrast, Treg administration promoted the functional recovery of five-toe spread and gait stance. hWJ-MSC also expressed high levels of the anti-inflammatory cytokines TGF-ß and IL-35. This study indicated that hWJ-MSC induce Treg development to modulate the balance between pro- and anti-inflammation at the injured sciatic nerve by secreting higher levels of anti-inflammatory cytokines.

Manual acupuncture relieves bile acid-induced itch in mice: the role of microglia and TNF-α.

Pruritus, or itch, is a frequent complaint amongst patients with cholestatic hepatobiliary disease and is difficult to manage, with many patients refractory to currently available antipruritic treatments. In this study, we examined whether manual acupuncture (MA) at particular acupoints represses deoxycholic acid (DCA)-induced scratching behavior and microglial activation and compared these effects with those induced by another pruritogen, 5'-guanidinonaltrindole (GNTI, a kappa opioid receptor antagonist). MA at Hegu (LI4) and Quchi (LI11) acupoints significantly attenuated DCA- and GNTI-induced scratching, whereas no such effects were observed at the bilateral Zusanli acupoints (ST36). Interestingly, GNTI-induced scratching was reduced similarly by both MA and electroacupuncture (EA) at the LI4 and LI11 acupoints. MA at non-acupoints did not affect scratching behavior. Intraperitoneal injection of minocycline (a microglial inhibitor) reduced GNTI- and DCA-induced scratching behavior. In Western blot analysis, subcutaneous DCA injection to the back of the neck increased spinal cord expression of ionized calcium-binding adapter molecule 1 (Iba1) and tumor necrosis factor-alpha (TNF-α) as compared with saline injection, while MA at LI4 and LI11 reduced these DCA-induced changes. Immunofluorescence confocal microcopy revealed that DCA-induced Iba1-positive cells with thicker processes emanated from the enlarged cell bodies, while this effect was attenuated by pretreatment with MA. It is concluded that microglia and TNF-α play important roles in the itching sensation and MA reduces DCA-induced scratching behavior by alleviating spinal microglial activation. MA may be an effective treatment for cholestatic pruritus.

Involvement of L-type Ca²âº channel and toll-like receptor-4 in nickel-induced interleukin-8 gene expression.

The metal nickel (Ni(2+)) is found everywhere in our daily lives, including coins, costume jewelry, and even nuts and chocolates. Nickel poisoning can cause inflammatory reactions, respiratory diseases, and allergic contact dermatitis. To clarify the mechanism by which nickel induces mediators of inflammation, we used the human acute monocytic leukemia THP-1 cell line as a model. Interleukin (IL)-8 promoter activity as well as gene expression were tested by luciferase assay and real-time polymerase chain reaction. The underlying mechanisms of nickel-induced IL-8 were investigated. We found that nickel induced IL-8 gene expression via the L-type Ca(2+) channel, Toll-like receptor-4 (TRL-4) and nuclear factor NF-κB signal transduction pathways. Nickel activated NF-κB expression through extracellular signal-regulated kinase 1/2 phosphorylation and then increased IL-8 expression. Thus, the L-type Ca(2+) channel and TRL-4 play important roles in nickel-induced inflammatory gene expressions.

Updated Bionomics of Toxorhynchites aurifluus and Toxorhynchites manicatus in Taiwan.

The larvae of the genus Toxorhynchites are typically found in sylvatic habitat environments. They have been proposed as potential biocontrol agents against disease vectors such as Aedes, specifically the larvae of Ae. aegypti and Ae. albopictus. The only 2 species of Toxorhynchites identified in Taiwan are Tx. aurifluus and Tx. manicatus, but there have been no published records of either species since 1984. In January 2014, we identified 2 4th-stage Tx. aurifluus larvae and 2 4th-stage Tx. manicatus larvae in artificial habitats close to dwellings in Guichong village, Pingtung County, Taiwan. Here we update the bionomics of the larvae of both species, including coexisting aquatic fauna, the physicochemical parameters of the larval habitats, and developmental time. We further compare the findings with past records.

Osteoporosis increases subsequent risk of gallstone: a nationwide population-based cohort study in Taiwan.

BACKGROUND: Osteopontin (OPN) is a pro-inflammatory cytokine which is expressed in various tissues. It participates in the bone remodeling process and stimulates bone resorption by osteoclasts. It is also a core protein of cholesterol gallstones. We hypothesized osteoporotic patients might have higher risk in developing gallstones and conducted a population-based study to examine the risk of developing gallstone in osteoporotic patients in Taiwan. METHODS: A total of 1,638 patients diagnosed with osteoporosis between 2003 and 2005 were identified in the National Health Insurance Research Database. A comparison cohort without osteoporosis (n =6,552) was randomly matched to each osteoporosis patient at a ratio of 4: 1 based on age and sex. A Cox proportional-hazards regression analysis was performed to evaluate the 5-year gallstone-free survival rates for the 2 cohorts. RESULTS: During the 5-year follow-up period, 114 and 311 cases of gallstone occurred in the osteoporosis and comparison cohorts, respectively. After adjusting for the confounders, the Cox regression analysis of the risk of gallstone in the osteoporosis and comparison cohorts yielded a hazard ratio of 1.35 (95% confidence interval: 1.07 - 1.69; p < 0 .01). CONCLUSION: Patients with osteoporosis in Taiwan have a higher risk of developing gallstone than the general population.

A mechanistic study on urine retention in d-amphetamine addicts.

Chronic amphetamine intake leads to neurogenic bladder and chronic urinary retention. The mechanism underlying persistent urinary retention is unclear. The pelvic-urethral reflex (PUR) is essential for the urethra to develop sufficient resistance to maintain urine continence, an important function of the urinary system. Recent studies on PUR activities have indicated that repetitive/tetanic stimulation of the pelvic afferent fibers induces spinal reflex potentiation (SRP) in PUR activities, which further increases urinary retention. In this study, results showed that test stimulation (TS, 1/30 Hz) evoked a baseline reflex activity, while repetitive stimulation (RS, 1 Hz) induced reflex potentiation in the external urethral sphincter. Intrathecal d-amphetamine (AMPH, 30 µM) did not but higher AMPH concentration (100 µM) induced SRP in TS-induced reflex activity. H89 (10 µM, a protein kinase A inhibitor), but not chelerythrine chloride (CTC, 10 µM, a protein kinase C inhibitor), prevented the 100 µM AMPH-elicited SRP. At 30 µM, forskolin, an activator of adenylyl cyclase, elicited SRP. The co-administration of 10 µM forskolin and 30 µM AMPH induced SRP in TS-induced reflex activity. These results implied that the repetitive/tetanic stimulation of the pelvic afferent fibers could induce SRP in PUR activities, so that the urethra can produce sufficient resistance and played a significant role in urinary retention. Findings in this study demonstrated that amphetamine could induce bladder dysfunction by triggering protein kinase A activation, and provide a practical basis for the development of treatment for amphetamine-associated urinary retention.

A Chinese herbal medicine, jia-wei-xiao-yao-san, prevents dimethylnitrosamine-induced hepatic fibrosis in rats.

Jia-wei-xiao-yao-san (JWXYS) is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN-) induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.

Assessing the impact of emergency measures in varied population density areas during a large dengue outbreak.

Background: The patterns of dengue are affected by many factors, including population density and climate factors. Densely populated areas could play a role in dengue transmission due to increased human-mosquito contacts, the presence of more diverse and suitable vector habitats and breeding sites, and changes in land use. In addition to population densities, climatic factors such as temperature, relative humidity, and precipitation have been demonstrated to predict dengue patterns. To control dengue, emergency measures should focus on vector management. Most approaches to assessing emergency responses to dengue risks involve applying simulation models or describing emergency activities and the results of implementing those responses. Research using real-world data with analytical methods to evaluate emergency responses to dengue has been limited. This study investigated emergency control measures associated with dengue risks in areas with high and low population densities, considering their different control capacities. Methodology: Data from the 2015 dengue outbreak in Kaohsiung City, Taiwan, were utilized. The government database provided information on confirmed dengue cases, emergency control measures, and climatic data. The study employed a distributed lag non-linear model (DLNM) to assess the effect of emergency control measures and their time lags on dengue risk. Principal findings: The findings revealed that in areas with high population density, the absence of emergency measures significantly elevated the risks of dengue. However, implementing emergency measures, especially a higher number, was associated with lower risks. In contrast, in areas with low population density, the risks of dengue were only significantly elevated at the 1st week lag if no emergency control measures were implemented. When emergency activities were carried out, the risks of dengue significantly decreased only for the 1st week lag. Conclusions: Our findings reveal distinct exposure-lag-response patterns in the associations between emergency control measures and dengue in areas with high and low population density. In regions with a high population density, implementing emergency activities during a significant dengue outbreak is crucial for reducing the risk. Conversely, in areas of low population density, the necessity of applying emergency activities may be less pronounced. The implications of this study on dengue management could provide valuable insights for health authorities dealing with limited resources.

IL-10 modified mRNA monotherapy prolongs survival after composite facial allografting through the induction of mixed chimerism.

Vascularized composite allotransplantation has great potential in face transplantation by supporting functional restoration following tissue grafting. However, the need for lifelong administration of immunosuppressive drugs still limits its wide use. Modified mRNA (modRNA) technology provides an efficient and safe method to directly produce protein in vivo. Nevertheless, the use of IL-10 modRNA-based protein replacement, which exhibits anti-inflammatory properties, has not been shown to prolong composite facial allograft survival. In this study, IL-10 modRNA was demonstrated to produce functional IL-10 protein in vitro, which inhibited pro-inflammatory cytokines and in vivo formation of an anti-inflammatory environments. We found that without any immunosuppression, C57BL/6J mice with fully major histocompatibility complex (MHC)-mismatched facial allografts and local injection of IL-10 modRNA had a significantly prolonged survival rate. Decreased lymphocyte infiltration and pro-inflammatory T helper 1 subsets and increased anti-inflammatory regulatory T cells (Tregs) were seen in IL-10 modRNA-treated mice. Moreover, IL-10 modRNA induced multilineage chimerism, especially the development of donor Treg chimerism, which protected allografts from destruction because of recipient alloimmunity. These results support the use of monotherapy based on immunomodulatory IL-10 cytokines encoded by modRNA, which inhibit acute rejection and prolong allograft survival through the induction of donor Treg chimerism.

Transient plasticity response is regulated by histone deacetylase inhibitor in oxygen-glucose deprivation condition.

BACKGROUND: The pathological form of synaptic plasticity, ischemic long-term potentiation (iLTP), induced by oxygen and glucose deprivation (OGD), is implicated in the acute phase of stroke with the potentiation of N-methyl-D-aspartate receptor (NMDAR). While there has been widespread attention on the excitatory system, a recent study reported that γ-aminobutyric acid (GABA)ergic system is also involved in iLTP. Valproic acid (VPA), a histone deacetylase inhibitor, protects against ischemic damage. However, whether VPA regulates early phase plasticity in ischemic stroke remains unknown. The present study aims to investigate the potential role and mechanism of VPA in ischemic stroke. METHODS: A brief exposure of OGD on the hippocampal slices and the induction of photothrombotic ischemia (PTI) were used as ex vivo and in vivo models of ischemic stroke, respectively. RESULTS: Using extracellular recordings, iLTP was induced in the hippocampal Schaffer collateral pathway following OGD exposure. VPA treatment abolished hippocampal iLTP via GABAA receptor enhancement and extracellular signal-regulated kinase (ERK) phosphorylation. Administration of VPA reduced brain infarct volume and motor dysfunction in mice with PTI. Moreover, VPA protected against ischemic injury by upregulating the GABAergic system and ERK phosphorylation, as well as by reducing of matrix metalloproteinase in a PTI-induced ischemic stroke model. CONCLUSIONS: Together, this study revealed the protection of VPA in ex vivo OGD-induced pathological form of neuroplasticity and in vivo PTI-induced brain damage and motor dysfunction through rescuing GABAergic deficiency and the pathological hallmarks of ischemia.

Dengue outbreaks in high-income area, Kaohsiung City, Taiwan, 2003-2009.

Kaohsiung City, a modern metropolis of 1.5 million persons, has been the focus of dengue virus activity in Taiwan for several decades. The aim of this study was to provide a temporal and spatial description of dengue virus epidemiology in Kaohsiung City by using data for all laboratory-confirmed dengue cases during 2003-2009. We investigated age- and sex-dependent incidence rates and the spatiotemporal patterns of all cases confirmed through passive or active surveillance. Elderly persons were at particularly high risk for dengue virus-related sickness and death. Of all confirmed cases, ≈75% were detected through passive surveillance activities; case-patients detected through active surveillance included immediate family members, neighbors, and colleagues of confirmed case-patients. Changing patterns of case clustering could be due to the effect of unmeasured environmental and demographic factors.

Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens-Johnson syndrome.

BACKGROUND: Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), are life-threatening drug hypersensitivities with robust immune responses to drugs. Despite the strong HLA predisposition to drug hypersensitivities, such as HLA-B∗1502 to carbamazepine (CBZ)-induced SJS/TEN, it remains unknown whether particular T-cell receptors (TCRs) participate in recognition of small drug/peptide-HLA complexes. OBJECTIVE: Using the strong HLA predisposition in patients with CBZ-induced SJS/TEN as a model, we aimed to study the use of TCR repertoire in patients with drug hypersensitivity. METHOD: We enrolled patients with CBZ-SJS/TEN, tolerant control subjects, and healthy subjects who had no history of CBZ exposure. We isolated PBMCs from the subjects, cultured CBZ-specific T cells, and globally investigated the expression level and third complementarity-determining region length distribution of the TCR profile. We further assessed the pathogenic role of the disease-specific clonotype using real-time PCR-based tests and functional analysis. RESULTS: On drug stimulation, CBZ-specific CD8(+) T cells were expanded in vitro and activated to release granulysin. Notably, VB-11-ISGSY was identified as the most predominant clonotype and shared among different subjects. This clonotype was present in 16 (84%) of 19 patients with SJS/TEN, absent in all 17 tolerant patients, and present at a low frequency in healthy subjects (4/29 [14%]). CBZ-specific cytotoxicity could be primed in vitro in the PBMCs of healthy subjects who are carriers of HLA-B∗1502 and VB-11-ISGSY; this cytotoxicity could be blocked by an anti-TCR-VB-11 antibody. Furthermore, a single T-cell clone expressing VA-22-FISGTY/VB-11-ISGSY showed significant cytotoxicity against HLA-B∗1502-positive antigen-presenting cells and CBZ. CONCLUSION: This study establishes the key role of the TCR in the pathogenic mechanism of SJS/TEN, explains why some HLA-B∗1502 carriers are tolerant to CBZ, and provides a biomarker profile for drug hypersensitivity.

How Spatial Epidemiology Helps Understand Infectious Human Disease Transmission.

Both directly and indirectly transmitted infectious diseases in humans are spatial-related. Spatial dimensions include: distances between susceptible humans and the environments shared by people, contaminated materials, and infectious animal species. Therefore, spatial concepts in managing and understanding emerging infectious diseases are crucial. Recently, due to the improvements in computing performance and statistical approaches, there are new possibilities regarding the visualization and analysis of disease spatial data. This review provides commonly used spatial or spatial-temporal approaches in managing infectious diseases. It covers four sections, namely: visualization, overall clustering, hot spot detection, and risk factor identification. The first three sections provide methods and epidemiological applications for both point data (i.e., individual data) and aggregate data (i.e., summaries of individual points). The last section focuses on the spatial regression methods adjusted for neighbour effects or spatial heterogeneity and their implementation. Understanding spatial-temporal variations in the spread of infectious diseases have three positive impacts on the management of diseases. These are: surveillance system improvements, the generation of hypotheses and approvals, and the establishment of prevention and control strategies. Notably, ethics and data quality have to be considered before applying spatial-temporal methods. Developing differential global positioning system methods and optimizing Bayesian estimations are future directions.

Modeling geographical invasions of Solenopsis invicta influenced by land-use patterns.

Research into geographical invasions of red imported fire ants (RIFAs) by anthropogenic disturbances has received much attention. However, little is known about how land-use change and the characteristics of roads with different land-use types are associated with the risk of RIFA successful invasion or remaining at the highest level of invasion (RIFA SIRH). Furthermore, it was often assumed in prior studies that the risk of RIFA SIRH had a linear association with the independent variables. However, a linear relationship may not reflect the actual circumstances. In this study, we applied linear and nonlinear approaches to assess how land-use types, distance from the nearest road, different land-use types, and spatial factors affect the risk of RIFA SIRH. The results showed that agricultural land, land for transportation usage, and areas that had undergone land-use change from 2014 to 2017 had greater odds of RIFA invasion than natural land cover. We also identified land for transportation usage and the area of land-use change from 2014 to 2017, had more than 60% of RIFA SIRH within 350 m and 150 m from the nearest road. This study provided important insights into RIFA invasions in an isolated island and the areas of control strategies implemented.