Multiplexable all-optical nonlinear activator for optical computing.

As an alternative solution to surpass electronic neural networks, optical neural networks (ONNs) offer significant advantages in terms of energy consumption and computing speed. Despite the optical hardware platform could provide an efficient approach to realizing neural network algorithms than traditional hardware, the lack of optical nonlinearity limits the development of ONNs. Here, we proposed and experimentally demonstrated an all-optical nonlinear activator based on the stimulated Brillouin scattering (SBS). Utilizing the exceptional carrier dynamics of SBS, our activator supports two types of nonlinear functions, saturable absorption and rectified linear unit (Relu) models. Moreover, the proposed activator exhibits large dynamic response bandwidth (∼11.24 GHz), low nonlinear threshold (∼2.29 mW), high stability, and wavelength division multiplexing identities. These features have potential advantages for the physical realization of optical nonlinearities. As a proof of concept, we verify the performance of the proposed activator as an ONN nonlinear mapping unit via numerical simulations. Simulation shows that our approach achieves comparable performance to the activation functions commonly used in computers. The proposed approach provides support for the realization of all-optical neural networks.

Facts and Hopes on Chimeric Cytokine Agents for Cancer Immunotherapy.

Cytokines are key mediators of immune responses that can modulate the antitumor activity of immune cells. Cytokines have been explored as a promising cancer immunotherapy. However, there are several challenges to cytokine therapy, especially a lack of tumor targeting, resulting in high toxicity and limited efficacy. To overcome these limitations, novel approaches have been developed to engineer cytokines with improved properties, such as chimeric cytokines. Chimeric cytokines are fusion proteins that combine different cytokine domains or link cytokines to antibodies (immunocytokines) or other molecules that can target specific receptors or cells. Chimeric cytokines can enhance the selectivity and stability of cytokines, leading to reduced toxicity and improved efficacy. In this review, we focus on two promising cytokines, IL2 and IL15, and summarize the current advances and challenges of chimeric cytokine design and application for cancer immunotherapy. Most of the current approaches focus on increasing the potency of cytokines, but another important goal is to reduce toxicity. Cytokine engineering is promising for cancer immunotherapy as it can enhance tumor targeting while minimizing adverse effects.

Mechanically Strong and Tough Poly(urea-urethane) Thermosets Capable of Being Degraded under Mild Condition.

The development of degradable polymeric materials such as degradable polyurethane or polyurea has been much highlighted for resource conservation and environmental protection. Herein, a facile strategy of constructing mechanically strong and tough poly(urea-urethane) (PUU) thermosets that can be degraded under mild conditions by using triple boron-urethane bonds (TBUB) as cross-linkers is demonstrated. By tailoring the molecular weight of the soft segment of the prepolymers, the mechanical performance can be finely controlled. Based on the cross-linking of TBUB units and hydrogen-binding interactions between TBUB linkages, the as-prepared PUU thermosets have excellent mechanical strength of ≈40.2 MPa and toughness of ≈304.9 MJ m-3 . Typically, the PBUU900 strip can lift a barbell with 60 000 times its own weight, showing excellent load-bearing capacity. Meanwhile, owing to the covalent cross-linking of TBUB units, all the PUU thermosets show initial decomposition temperatures over 290 °C, which are comparable to those of the traditional thermosets. Moreover, the TBUB cross-linked PUU thermosets can be easily degraded in a mild acid solution. The small pieces of the PBUU sample can be fully decomposed in 1 m HCl/THF solution for 3.5 h at room temperature.

Advantages of Transmuscular Quadratus Lumborum Block via Subfascial Approach Versus Extrafascial Approach for Postoperative Analgesia After Laparoscopic Cholecystectomy: A Randomized Controlled Study.

OBJECTIVE: We aimed to compare the analgesic effect and incidence of lower limb weakness of transmuscular quadratus lumborum (TQL) block via subfascial approach with that via extrafascial after laparoscopic cholecystectomy (LC). METHODS: Eighty patients undergoing LC were randomized to receive ultrasound-guided bilateral TQL block via subfascial (subfascial group) or extrafascial (extrafascial group) using 30 mL of 0.33% ropivacaine unilaterally. Pain scores of port sites while rest and coughing at 1, 6, 12, 24, 36, and 48 hours postoperatively as primary outcome were compared. Modified Lovett Rating Scale, ambulatory dependency, and rescue analgesia requirement was also compared. RESULTS: The pain score of the subxiphoid and of the right subcostal port site for up to the postoperative 36 hours (2 [1 to 2]) and 24 hours (2 [2 to 3]) in the subfascial group was significantly lower than that in extrafascial group (2 [2 to 2] and 3 [2.25 to 4]). Up to postoperative 24 hours, the rescue analgesia requirement in subfascial group was significantly lower than that in extrafascial group, namely less fentanyl consumption and parecoxib (1.3 [±5.5] µg vs. 5.6 [±10.6] µg; 17.5% vs. 37.5%). The ratio of patients with LRS score of 6 at postoperative 1 hour (65.0%), and with dependent ambulation at postoperative 1 and 6 hours in subfascial group (15.0% and 0.0%) was significantly lower than that in extrafascial group (10.0%, 80.0%, and 17.5%). CONCLUSION: TQL block via subfascial had the advantages of better analgesic effect and less lower limbs weakness after LC over that via extrafascial.

Study on Welding Deformation and Optimization of Fixture Scheme for Thin-Walled Flame Cylinder.

In this paper, the best fixture scheme for the TIG welding torch of nickel-base solid solution superalloy GH3536 in the welding process is explored. First of all, to meet the extremely high-dimensional accuracy requirements of the flame cylinder, a multifield coupling analysis model based on the flame cylinder is established on SYSWELD software. By studying the stress and deformation of welded parts under different line constraint positions and applied pressure, the trend of welding deformation is obtained, and the relevant mathematical model is established based on this. Finally, the particle swarm optimization (PSO) algorithm is used to calculate the best fixture scheme to make the welding stress and deformation better. The simulation results show that the welding deformation is negatively related to the line constraint distance and positively related to the applied pressure. According to the optimized clamping scheme of PS0, through simulation calculation, the average axial deformation is reduced by 82.5%, the maximum radial shrinkage deformation is reduced by 60.6%, and the maximum residual stress is reduced by 60.3%. Finally, it is verified by the flame barrel experiment that it meets the acceptance requirements and successfully solves the problem of serious axial shrinkage during the TIG welding of the outer ring of the flame barrel.

Porous geopolymer with controllable interconnected pores-a viable permeable reactive barrier filler for lead pollutant removal.

Most of the commonly used traditional permeable reactive barrier (PRB) fillers have many drawbacks, such as poor retention of hydraulic conductivity, high cost, and a complex preparation process. Porous geopolymers (PGPs) with controllable pore structures could circumvent these drawbacks owing to their high adsorption capacity, cost-effective synthesis, and good chemical stability. In this study, based on our previous research, the "foaming-liquid film" balance control method was proposed and used to fabricate three PGPs with gradient pore connectivity. The influence of pore structure on the Pb2+ removal performance and migration mechanism were investigated by conducting both batch and column experiments. Closed, dead-end, capillary, and interconnected pores exist in the PGPs, and results indicated that interconnected pores effectively promote the migration of solute in the main flow channels to the deeper matrix, thereby enhancing the long-term dynamic removal efficiency. At breakthrough, the Pb2+ uptake of PGP-3 reached 146 mg g-1. Further, the proposed "foaming-liquid film" balance control method is effective to prepare PGPs with controllable connectivity, and the PGP-PRBs with a high proportion of interconnected pores exhibit excellent performance for the removal of heavy metals, which is advantageous for their future applications in groundwater decontamination.

Optimization of PBFT Algorithm Based on QoS-Aware Trust Service Evaluation.

In service-transaction scenarios, blockchain technology is widely used as an effective tool for establishing trust between service providers and consumers. The consensus algorithm is the core technology of blockchain. However, existing consensus algorithms, such as the practical Byzantine fault tolerance (PBFT) algorithm, still suffer from high resource consumption and latency. To solve this problem, in this study, we propose an improved PBFT blockchain consensus algorithm based on quality of service (QoS)-aware trust service evaluation for secure and efficient service transactions. The proposed algorithm, called the QoS-aware trust practical Byzantine fault tolerance (QTPBFT) algorithm, efficiently achieves consensus, significantly reduces resource consumption, and enhances consensus efficiency. QTPBFT incorporates a QoS-aware trust service global evaluation mechanism that implements service reliability ranking by conducting a dynamic evaluation according to the real-time performance of the services. To reduce the traffic of the blockchain, it uses a mechanism that selects nodes with higher values to form a consensus group that votes for consensus according to the global evaluation result of the trust service. A practical protocol is also constructed for the proposed algorithm. The results of extensive simulations and comparison with other schemes verify the efficacy and efficiency of the proposed scheme.

Blocking GARP-mediated activation of TGF-ß1 did not alter innate or adaptive immune responses to bacterial infection or protein immunization in mice.

Transmembrane protein GARP binds latent TGF-ß1 to form GARP:(latent)TGF-ß1 complexes on the surface of several cell types including Tregs, B-cells, and platelets. Upon stimulation, these cells release active TGF-ß1. Blocking TGF-ß1 activation by Tregs with anti-GARP:TGF-ß1 mAbs overcomes resistance to PD1/PD-L1 blockade and induces immune-mediated regressions of murine tumors, indicating that Treg-derived TGF-ß1 inhibits anti-tumor immunity. TGF-ß1 exerts a vast array of effects on immune responses. For example, it favors differentiation of TH17 cells and B-cell switch to IgA production, two important processes for mucosal immunity. Here, we sought to determine whether treatment with anti-GARP:TGF-ß1 mAbs would perturb immune responses to intestinal bacterial infection. We observed no aggravation of intestinal disease, no systemic dissemination, and no alteration of innate or adaptative immune responses upon oral gavage of C. rodentium in highly susceptible Il22r-/- mice treated with anti-GARP:TGF-ß1 mAbs. To examine the effects of GARP:TGF-ß1 blockade on Ig production, we compared B cell- and TH cell- responses to OVA or CTB protein immunization in mice carrying deletions of Garp in Tregs, B cells, or platelets. No alteration of adaptive immune responses to protein immunization was observed in the absence of GARP on any of these cells. Altogether, we show that antibody-mediated blockade of GARP:TGF-ß1 or genetic deletion of Garp in Tregs, B cells or platelets, do not alter innate or adaptive immune responses to intestinal bacterial infection or protein immunization in mice. Anti-GARP:TGF-ß1 mAbs, currently tested for cancer immunotherapy, may thus restore anti-tumor immunity without severely impairing other immune defenses. PRéCIS: Immunotherapy with GARP:TGF-ß1 mAbs may restore anti-tumor immunity without impairing immune or inflammatory responses required to maintain homeostasis or host defense against infection, notably at mucosal barriers.

A review of rotavirus vaccine use in Asia and the Pacific regions: challenges and future prospects.

INTRODUCTION: Rotavirus infection causes a significant proportion of diarrhea disease burden in children <5 years of age in Asia and the Pacific regions. The World Health Organization recommends that rotavirus vaccination should be included in national immunization programs to prevent rotavirus gastroenteritis (RVGE). AREAS COVERED: A literature review was performed to identify and summarize published evidence on RVGE epidemiology and status of rotavirus vaccine use, including the impact and cost-effectiveness of rotavirus vaccination programs in Asia and the Pacific regions (49 countries) during the period 2000-2018. EXPERT OPINION: Rotavirus vaccination programs have successfully reduced the burden of RVGE in many countries. However, such programs still do not exist in most Asia-Pacific countries, and therefore the burden of RVGE remains high in children <5 years of age. Challenges to vaccine implementation include a lack of surveillance data; safety concerns around intussusception; a general lack of awareness about RVGE disease epidemiology and vaccines among physicians, policy-makers, and parents; insufficient cost-effectiveness analyses; and potential issues with vaccine affordability including vaccination costs and lack of political will. Recommendations to overcome these challenges include developing cost-effectiveness analyses for more diverse national and regional settings, providing non-governmental support for low-income countries, and improving advocacy efforts.

PLAIN LANGUAGE SUMMARYWhat is the context?Rotavirus (RV) infection causes acute gastroenteritis (GE) in children under 5 years of age.Rotavirus vaccination (RVV) implementation has been slow in Asia and the Pacific (AP) regions, which could be responsible for the region falling behind in their fight against RVGE.What is new?RVV via national immunization programs (NIPs) is available in 8/49 countries and through the private market or non-governmental support in other countries. Coverage rates vary between countries, possibly driven by the mechanism through which RVV is available.A substantial positive impact of RVV on RVGE disease burden with a very low risk of intestinal intussusception for up to 7 days after RVV has been documented in the AP regions.Economic evaluation studies, mainly cost-effectiveness analyses, predict a significant reduction in treatment costs related to RVGE and its complications showing that RVV is good value for money.What is the impact?The prospect of continued safe and effective use of RVV in the AP regions is promising.Challenges to RVV implementation include establishing evidence of burden of disease, poor awareness of rotavirus vaccines, limited evidence from cost-effectiveness analyses from several countries, issues of affordability of the vaccine and a lack of political will.Recommendations for RVV implementation into the NIPs include conducting clinical and cost-effectiveness studies in countries where these are not available, establishing reliable surveillance mechanisms, providing non-governmental support for low-income countries and improving advocacy efforts.Maintenance of high vaccination coverage is needed in countries that have implemented national RVV programs.Graphical abstract[Formula: see text].

Cost-effectiveness evaluation of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine for children in Taiwan.

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) and non-typeable Haemophilus influenzae (NTHi) are substantial contributors to morbidity and mortality of diseases including invasive pneumococcal diseases (IPDs), pneumonia and acute otitis media (AOM) worldwide. In Taiwan, 10-valent pneumococcal polysaccharide and NTHi protein D conjugate vaccine (PHiD-CV) and 13-valent pneumococcal conjugate vaccine (PCV13) are licensed in children against pneumococcal disease. In addition to S. pneumoniae, clinical trials suggest efficacy of PHiD-CV against NTHi AOM. This study aims at evaluating the cost-effectiveness of a 2 + 1 schedule of PHiD-CV vs. PCV13 2 + 1 in the universal mass vaccination program of infants in Taiwan. METHODS: A published Markov cohort model was adapted to simulate the epidemiological burden of IPD, pneumonia and AOM for a birth cohort in Taiwan over 10 years. The probability of entering a specific health state was based on the incidence rate of the diseases. Only direct medical costs were included, and costs and outcomes were discounted annually. Vaccine efficacy assumptions were based on published data and validated by a panel of independent experts. Clinical, epidemiological, and serotype distribution data were based on locally published data or the National Health Insurance Research Database. Price parity of vaccines was assumed. Published pneumococcal disease-related disutility weights were used due to lack of local data. Incremental cost-effectiveness ratio was calculated and benchmarked against the recommended threshold in Taiwan. Extensive one-way sensitivity analysis, alternative scenarios and probabilistic sensitivity analysis were performed to test the robustness of the results. RESULTS: PHiD-CV would potentially reduce the number of NTHi-related AOM cases substantially and prevent comparable IPD and pneumonia-related cases and deaths compared to PCV13. Over a 10-year horizon, PHiD-CV is estimated to dominate PCV13, saving 6.7 million New Taiwan Dollars (NTD) and saving 21 quality-adjusted life years. The result was robust over a wide range of sensitivity analyses. The dominance of PHiD-CV was demonstrated in 90.5% of the simulations. CONCLUSIONS: PHiD-CV 2 + 1 would provide comparable prevention of IPD, pneumonia cases and additional reduction of NTHi-AOM cases, and is considered dominant compared with PCV13 2 + 1 in Taiwan.

Combined ultrasound and nerve stimulator-guided deep nerve block may decrease the rate of local anesthetics systemic toxicity: a randomized clinical trial.

BACKGROUND: Ultrasound guidance might decrease the incidence of local anesthetics systemic toxicity (LAST) for many peripheral nerve blocks compared with nerve stimulator guidance. However, it remains uncertain whether ultrasound guidance is superior to nerve stimulator guidance for deep nerve block of the lower extremity. This study was designed to investigate whether deep nerve block with ultrasound guidance would decrease the incidence of LAST compared with that with nerve stimulator guidance, and to identify associated risk factors of LAST. METHODS: Three hundred patients undergoing elective lower limb surgery and desiring lumbar plexus blocks (LPBs) and sciatic nerve blocks (SNBs) were enrolled in this study. The patients were randomly assigned to receive LPBs and SNBs with ultrasound guidance (group U), nerve stimulator guidance (group N) or dual guidance (group M). The primary outcome was the incidence of LAST. The secondary outcomes were the number of needle redirection, motor and sensory block onset and nerve distribution restoration time, as well as associated risk factors. RESULTS: There were 18 patients with LAST, including 12 in group U, 4 in group N and 2 in group M. By multiple comparisons among the three groups, we found that the incidence of LAST in group U (12%) was significantly higher than that in group N (4%)(P = 0.037) and group M(2%)(P = 0.006). The OR of LAST with hepatitis B (HBV) infection and the female sex was 3.352 (95% CI,1.233-9.108, P = 0.013) and 9.488 (95% CI,2.142-42.093, P = 0.0004), respectively. CONCLUSIONS: Ultrasound guidance, HBV infection and the female sex were risk factors of LAST with LPBs and SNBs. For patients infected with HBV or female patients receiving LPBs and SNBs, we recommended that combined ultrasound and nerve stimulator guidance should be used to improve the safety. TRIAL REGISTRATION: This study was approved by the Ethical Committee of the First Affiliated Hospital of Army Medical University. The protocol was registered prospectively with the Chinese Clinical Trial Registry ( ChiCTR-IOR-16008099 ) on March 15, 2016.

Economic Evaluation of Human Rotavirus Vaccine in Thailand.

INTRODUCTION: Rotavirus gastroenteritis is the leading cause of severe diarrhoea among young children < 5 years old. Previous cost-effectiveness analyses on rotavirus (RV) vaccination in Thailand have generated conflicting results. The aim of this current study is to evaluate the economic impact of introducing RV vaccination in Thailand, using updated Thai epidemiological and cost data. METHODS: Both cost-utility analysis (CUA) and budget impact analysis (BIA) of human rotavirus vaccine (HRV) under a universal mass vaccination (UMV) programme were conducted. A published static, deterministic, cross-sectional population model was adapted to assess costs and health outcomes associated with RV vaccination among Thai children < 5 years old during 1 year for CUA and over a 5-year period (2019-2023) for BIA. Data identified through literature review were incorporated into the model after consultation with local experts. Base case CUA was conducted from a societal perspective with quality-adjusted life year (QALY) discounted at 3% annually. Scenario analyses as well as one-way and probabilistic sensitivity analyses were conducted to assess the robustness of the base case CUA results. Costs were updated to 2017. RESULTS: At 99% coverage, HRV vaccination would substantially reduce RV-related disease burden. With an incremental cost-effectiveness ratio (ICER) of Thai baht (THB) 49,923/QALY gained, HRV vaccination versus no vaccination was cost-effective when assessed against a local threshold of THB 160,000/QALY gained. Scenario and sensitivity analyses confirmed the cost-effectiveness with all resultant ICERs falling below the willingness-to-pay threshold. HRV use in the UMV programme was estimated to result in a net expenditure of about THB 255-281 million to the Thai government in the 5th year of the programme, depending on vaccine uptake. CONCLUSION: HRV vaccination is estimated to be cost-effective in Thailand. The budget impact following inclusion of HRV into the UMV programme is expected to be partially offset by substantial reductions in RV-related disease costs. FUNDING: GlaxoSmithKline Biologicals SA GSK STUDY IDENTIFIER: HO-17-18213.

An effective dendritic cell-based vaccine containing glioma stem-like cell lysate and CpG adjuvant for an orthotopic mouse model of glioma.

Owing to the limited therapeutic efficacy of glioma vaccines, new strategies are required to improve cancer vaccines. Our study aimed to assess the therapeutic efficacy of a glioma vaccine called STDENVANT. This vaccine, comprising glioma stem-like cell (GSC) lysate, dendritic cells (DCs), and Toll-like receptor (TLR) 9 agonist CpG motif-containing oligodeoxynucleotides (CpG ODNs), was assessed using a GL261-C57BL/6 orthotopic mouse model of glioma. STDENVANT markedly improved survival and tumor regression by enhancing anti-tumor immune function. Moreover, STDENVANT upregulated programmed death 1 (PD-1) and its ligand PD-L1 on effector T cells, DCs, and glioma tissues, resulting in the accumulation of regulatory T (Treg) cells in the brain and lymph nodes. Combinatorial administration of anti-PD-L1 antibody and STDENVANT conferred a greater survival advantage and decreased the Treg cell population in the brain. The present results indicate that PD-L1 blockade can promote tumor regression via STDENVANT in a mouse model of glioma, and combinatorial administration of anti-PD-L1 antibody and STDENVANT increases the therapeutic anti-tumor efficacy of treatment.

Complete genome sequence of Bacillus velezensis ZY-1-1 reveals the genetic basis for its hemicellulosic/cellulosic substrate-inducible xylanase and cellulase activities.

Bacillus velezensis ZY-1-1 was isolated from the larval gut of the lignocellulose-rich diet-fed scarab beetle, Holotrichia parallela, and confirmed to possess extremely high xylanase (48153.8 ± 412.1 U/L) and relatively moderate cellulase activity (610.1 ± 8.2 U/L). Notably, these xylanase and cellulase activities were enhanced by xylan (1.4 and 5.8-fold, respectively) and cellulose (1.1 and 3.5-fold, respectively), which indicated the hemicellulosic/cellulosic substrate-inducible lignocellulolytic activities of this strain. The complete genome of B. velezensis ZY-1-1 comprises of 3,899,251 bp in a circular chromosome with a G + C content of 46.6%. Among the predicted 3688 protein-coding genes, 24 genes are involved in the degradation of lignocellulose and other polysaccharides, including 8, 7 and 2 critical genes for the degradation of xylan, cellulose and lignin, respectively. This genome-based analysis will facilitate our understanding of the mechanism underlying the biodegradation of lignocellulose and the biotechnological application of this novel lignocellulolytic bacteria or related enzymes.

A Cost-Effectiveness Analysis of the 10-Valent Pneumococcal Non-Typeable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) Compared to the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) for Universal Mass Vaccination Implementation in New Zealand.

OBJECTIVES: Invasive pneumococcal disease (IPD), pneumonia and acute otitis media (AOM) still represent a significant medical burden in children < 5 years of age in New Zealand (NZ), with marked disparities across socio-economic and ethnic groups. This cost-effectiveness evaluation aims to compare the potential impact of two childhood universal immunisation strategies: vaccination with a 3 + 1 schedule of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix, GSK) and the 13-valent pneumococcal conjugate vaccine (PCV13, Prevenar 13, Pfizer). METHODS: A static Markov-process cohort model was used to simulate the epidemiological and economic burden of pneumococcal diseases on a single-birth cohort over its lifetime. Costs and outcomes were discounted annually at 3.5%. Epidemiological and cost inputs were extracted from the most recently available NZ data, or derived from the most relevant reference countries' sources. The most updated evidence on the efficacies of the corresponding vaccines were used, particularly the significant effectiveness for PHiD-CV against IPD caused by serotype 19A. RESULTS: The model estimated that both vaccines have a broadly comparable impact on IPD-related diseases and pneumonia. Due to the additional benefits possible through broader impact on AOM, PHiD-CV is estimated to potentially provide additional discounted cost offsets of approximately NZD 0.8 million over the lifetime of the birth cohort. CONCLUSIONS: To ensure health equity in children, given the substantial burden of pneumonia and AOM, decision-makers should also take into account the impact of PCVs on these diseases for decisions relating to routine infant immunization. GSK STUDY IDENTIFIER: HO-15-16775.

Burden of hospitalized childhood community-acquired pneumonia: A retrospective cross-sectional study in Vietnam, Malaysia, Indonesia and the Republic of Korea.

BACKGROUND: Few studies describe the community-acquired pneumonia (CAP) burden in children in Asia. We estimated the proportion of all CAP hospitalizations in children from nine hospitals across the Republic of Korea (high-income), Indonesia, Malaysia (middle-income), and Vietnam (low/middle-income). METHODS: Over a one or two-year period, children <5 years hospitalized with CAP were identified using ICD-10 discharge codes. Cases were matched to standardized definitions of suspected (S-CAP), confirmed (C-CAP), or bacterial CAP (B-CAP) used in a pneumococcal conjugate vaccine efficacy study (COMPAS). Median total direct medical costs of CAP-related hospitalizations were calculated. RESULTS: Vietnam (three centers): 7591 CAP episodes were identified with 4.3% (95% confidence interval 4.2;4.4) S-CAP, 3.3% (3.2;3.4) C-CAP and 1.4% (1.3;1.4) B-CAP episodes of all-cause hospitalization in children aged <5 years. The B-CAP case fatality rate (CFR) was 1.3%. Malaysia (two centers): 1027 CAP episodes were identified with 2.7% (2.6;2.9); 2.6% (2.4;2.8); 0.04% (0.04;0.1) due to S-CAP, C-CAP, and B-CAP, respectively. One child with B-CAP died. Indonesia (one center): 960 CAP episodes identified with 18.0% (17.0;19.1); 16.8% (15.8;17.9); 0.3% (0.2;0.4) due to S-CAP, C-CAP, and B-CAP, respectively. The B-CAP CFR was 20%. Korea (three centers): 3151 CAP episodes were identified with 21.1% (20.4;21.7); 11.8% (11.2;12.3); 2.4% (2.1;2.7) due to S-CAP, C-CAP, and B-CAP, respectively. There were no deaths. COSTS: CAP-related hospitalization costs were highest for B-CAP episodes: 145.00 (Vietnam) to 1013.3 USD (Korea) per episode. CONCLUSION: CAP hospitalization causes an important health and cost burden in all four countries studied (NMRR-12-50-10793).

Cost-effectiveness analysis of infant pneumococcal vaccination with PHiD-CV in Korea.

BACKGROUND: Streptococcus pneumoniae and non-typeable Haemophilus influenzae (NTHi) can cause invasive pneumococcal diseases (IPD), pneumonia, and acute otitis media (AOM). Both the 10-valent pneumococcal NTHi protein D conjugate vaccine (PHiD-CV) and the 13-valent pneumococcal conjugate vaccine (PCV-13) are included in the National Immunization Program for infants in Korea. This study aimed to evaluate the cost-effectiveness of the 3+1 schedule of PHiD-CV versus that of PCV-13 for National Immunization Program in Korea. METHODS: A published Markov model was adapted to evaluate the cost-effectiveness of vaccinating the 2012 birth cohort with PHiD-CV vs. PCV-13 from the Korean government perspective over 10 y. Best available published data were used for epidemiology, vaccine efficacy and disutilities. Data on incidence and direct medical costs were taken from the national insurance claims database. Sensitivity analyses were conducted to explore the robustness of the results. RESULTS: PHiD-CV was projected to prevent an additional 195,262 cases of pneumococcal diseases and NTHi-related diseases vs. PCV-13, with a substantially greater reduction in NTHi-related AOM and a comparable reduction in IPD and community-acquired pneumonia. Parity-priced PHiD-CV generated a health gain of about 844 quality-adjusted life years and a total cost-saving of approximately 4 million United States Dollars (USD) over 10 y. 93% of probabilistic simulations found PHiD-CV 3+1 to be the dominant vaccine option. CONCLUSION: Compared to PCV-13, PHiD-CV was projected to provide similar prevention against IPD and community-acquired pneumonia but would prevent more cases of AOM. Parity-priced PHiD-CV was anticipated to generate substantial cost-savings and health benefits vs. PCV-13 in Korea.

Grape seed proanthocyanidins induce mitochondrial pathway-mediated apoptosis in human colorectal carcinoma cells.

Grape seed proanthocyanidins (GSPs) have been reported to possess a wide array of pharmacological and biochemical properties. Recently, GSPs have been reported to inhibit various types of colorectal cancer; however, the mechanism(s) involved remain unclear. The present study investigated the effects of GSPs on HCT-116 human colorectal carcinoma cell line. Exposure of these cells to GSPs for 48 h resulted in a significant concentration-dependent inhibition of cell viability. Further investigation indicated that GSPs induced apoptosis of these cells. Analyses of mRNA expression levels using reverse transcription-quantitative polymerase chain reaction and protein expression levels by western blotting revealed that this was associated with increased expression levels of p53 tumor suppressor protein, cytochrome c, and pro-apoptotic proteins, apoptosis regulator Bax (Bax) and Bcl-2 homologous antagonist/killer. Furthermore, decreased expression levels of the anti-apoptotic protein, B cell lymphoma-2 and activation of caspase-2, caspase-3 and caspase-9 were demonstrated. GSP-induced loss of mitochondrial membrane potential was also detected by JC-1 assay. These findings suggested that GSPs induced colon cancer cell apoptosis via the mitochondrial signaling pathway. This provided evidence indicating that GSPs may provide potential chemotherapeutic agents for colorectal cancer.

Cost-effectiveness analysis of a universal mass vaccination program with a PHiD-CV 2+1 schedule in Malaysia.

BACKGROUND: Currently, two pediatric pneumococcal conjugate vaccines are available in the private market of Malaysia-13-valent pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide and non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). This study aimed to evaluate the cost-effectiveness of a universal mass vaccination program with a PHiD-CV 2+1 schedule versus no vaccination or with a PCV13 2+1 schedule in Malaysia. METHODS: A published Markov cohort model was adapted to evaluate the epidemiological and economic consequences of programs with no vaccination, a PHiD-CV 2+1 schedule or a PCV13 2+1 schedule over a 10-year time horizon. Disease cases, deaths, direct medical costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated. Locally published epidemiology and cost data were used whenever possible. Vaccine effectiveness and disutility data were based on the best available published data. All data inputs and assumptions were validated by local clinical and health economics experts. Analyses were conducted from the perspective of the Malaysian government for a birth cohort of 508,774. Costs and QALYs were discounted at 3% per annum. One-way and probabilistic sensitivity analyses were performed. RESULTS: Compared with no vaccination, a PHiD-CV 2+1 program was projected to prevent 1109 invasive pneumococcal disease (IPD), 24,679 pneumonia and 72,940 acute otitis media (AOM) cases and 103 IPD/pneumonia deaths over 10 years, with additional costs and QALYs of United States dollars (USD) 30.9 million and 1084 QALYs, respectively, at an ICER of USD 28,497/QALY. Compared with a PCV13 2+1 program, PHiD-CV 2+1 was projected to result in similar reductions in IPD cases (40 cases more) but significantly fewer AOM cases (30,001 cases less), with cost savings and additional QALYs gained of USD 5.2 million and 116 QALYs, respectively, demonstrating dominance over PCV13. Results were robust to variations in one-way and probabilistic sensitivity analyses. CONCLUSIONS: A PHiD-CV 2+1 universal mass vaccination program could substantially reduce pneumococcal disease burden versus no vaccination, and was expected to be cost-effective in Malaysia. A PHiD-CV 2+1 program was also expected to be a dominant choice over a PCV13 2+1 program in Malaysia.