Lingual bracket transfer accuracy of double vacuum-formed indirect bonding tray using 3D-printed model: an in vivo study.

INTRODUCTION: This study aimed to assess the transfer accuracy of a digital indirect bonding method for lingual brackets using double vacuum-formed trays in vivo. METHODS: Twenty-five patients in need of lingual orthodontic treatment were consecutively recruited. Bracket placement was performed on ideal setups, followed by fabricating indirect bonding trays through vacuum-forming on 3-dimensional printed models. Transfer accuracy was measured at each bracket after superimpositions of postbonding scans and reference data. One-tailed t tests were used to determine whether bracket deviations were within the limit of 0.5 mm and 2° for linear and angular dimensions, respectively. RESULTS: A total of 611 lingual brackets were evaluated. Mean linear transfer errors were 0.06 mm, 0.09 mm, and 0.12 mm, with frequencies of deviations within the 0.5 mm limit of 99.7%, 99.8%, and 98.0% for mesiodistal, buccolingual, and occlusogingival dimensions, respectively. Regarding angular measurements, mean transfer errors were 1.28°, 1.73°, and 2.96°, with frequencies of deviations within the 2° limit of 81.0%, 68.9%, and 51.1% for rotation, tip, and torque, respectively. Mean errors fell within the clinically accepted limits for all linear dimensions and rotation but exceeded the limit for tip and torque. CONCLUSIONS: Lingual bracket indirect bonding using double vacuum-formed trays fabricated on 3-dimensional printed models has high transfer accuracy in the mesiodistal, buccolingual, and occlusogingival dimensions and rotation. However, the transfer of tip and torque is less accurate.

Periodontitis and Preeclampsia in Pregnancy: A Systematic Review and Meta-Analysis.

OBJECTIVES: A conflicting body of evidence suggests localized periodontal inflammation spreads systemically during pregnancy inducing adverse pregnancy outcomes. This systematic review and meta-analysis aim to specifically evaluate the relationship between periodontitis and preeclampsia. METHODS: Electronic searches were carried out in Medline, Pubmed, Embase, Lilacs, Cochrane Controlled Clinical Trial Register, CINAHL, ClinicalTrials.gov, and Google Scholar with no restrictions on the year of publication. We identified and selected observational case-control and cohort studies that analyzed the association between periodontal disease and preeclampsia. This meta-analysis was conducted following the PRISMA checklist and MOOSE checklist. Pooled odds ratios, mean difference, and 95% confidence intervals were calculated using the random effect model. Heterogeneity was tested with Cochran's Q statistic. RESULTS: Thirty studies including six cohort- and twenty-four case-control studies were selected. Periodontitis was significantly associated with increased risk for preeclampsia (OR 3.18, 95% CI 2.26 - 4.48, p < 0.00001), especially in a subgroup analysis including cohort studies (OR 4.19, 95% CI 2.23 - 7.87, p < 0.00001). The association was even stronger in a subgroup analysis with lower-middle-income countries (OR 6.70, 95% CI 2.61 - 17.19, p < 0.0001). CONCLUSIONS: Periodontitis appears as a significant risk factor for preeclampsia, which might be even more pronounced in lower-middle-income countries. Future studies to investigate if maternal amelioration of periodontitis prevents preeclampsia might be warranted.

Development of a Solar-Powered IoT-Based Instrument for Automatic Measurement of Water Clarity.

Water clarity is the most common indicator of water quality. The purpose of the study was to develop an instrument which can automatically measure water clarity in place of manual measurement by Secchi disk. The instrument is suspended by buoys at the water surface and uses solar energy to measure the light intensity of LED bulbs after passing through a water column; the result is then converted to Secchi depth by using a regression function. Measurement data are stored in a cloud server so that mobile users can access via an Internet connection. Three experiments were conducted to examine the instrument performance: (i) to ensure light intensity of the LED bulbs is strong enough to pass through the water column; (ii) to determine the regression relationship between the measured light intensity of the instrument and Secchi depth; and (iii) to evaluate the coefficient of variation (CV) of the measured water clarity when using our instrument and a conventional Secchi disk. Experiment results show that the measured values of light intensity are stable with the average CV = 5.25%. Moreover, although there are slight differences between the Secchi depth measured by our instrument and those measured by Secchi disk, the measurements by our instrument can efficiently replace the measurements by conventional Secchi disk, which can be affected by weather conditions as well as by human subjectivity.

An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem/Stromal Cells.

Bone marrow mesenchymal stem/stromal cells (BMSCs), which are known as multipotent cells, are widely used in the treatment of various diseases via their self-renewable, differentiation, and immunomodulatory properties. In-vitro and in-vivo studies have supported the understanding mechanisms, safety, and efficacy of BMSCs therapy in clinical applications. The number of clinical trials in phase I/II is accelerating; however, they are limited in the size of subjects, regulations, and standards for the preparation and transportation and administration of BMSCs, leading to inconsistency in the input and outcome of the therapy. Based on the International Society for Cellular Therapy guidelines, the characterization, isolation, cultivation, differentiation, and applications can be optimized and standardized, which are compliant with good manufacturing practice requirements to produce clinical-grade preparation of BMSCs. This review highlights and updates on the progress of production, as well as provides further challenges in the studies of BMSCs, for the approval of BMSCs widely in clinical application.

Zika virus in Vietnam, Laos, and Cambodia: are there health risks for travelers?

Vietnam, Laos, and Cambodia have reported first cases of Zika virus (ZIKV) infection since 2010 (Cambodia) and 2016 (Vietnam and Laos). One case of ZIKV-related microcephaly was recognized among a hundred infected cases in these areas, raising a great concern about the health risk related to this virus infection. At least 5 cases of ZIKV infection among travelers to Vietnam, Laos, and Cambodia were recorded. It is noticeable that ZIKV in these areas can cause birth defects. This work aims to discuss the current epidemics of ZIKV in Vietnam, Laos, and Cambodia and update the infection risk of ZIKV for travelers to these areas.

Zoonotic diseases from birds to humans in Vietnam: possible diseases and their associated risk factors.

In recent decades, exceeding 60% of infectious cases in human beings are originated from pathogenic agents related to feral or companion animals. This figure continues to swiftly increase due to excessive exposure between human and contaminated hosts by means of applying unhygienic farming practices throughout society. In Asia countries-renowned for lax regulation towards animal-trading markets-have experienced tremendous outbreaks of zoonotic diseases every year. Meanwhile, various epidemic surges were first reported in the residential area of China-one of the largest distributor of all animal products on the planet. Some noticeable illnesses comprising of A/H5N1 or H7N9-known as avian influenza which transmitted from poultry and also wild birds-have caused inevitable disquiet among inhabitants. Indeed, poultry farming industry in China has witnessed dynamic evolution for the past two decades, both in quantity and degree of output per individual. Together with this pervasive expansion, zoonotic diseases from poultry have incessantly emerged as a latent threat to the surrounding residents in entire Asia and also European countries. Without strict exporting legislation, Vietnam is now facing the serious problem in terms of poultry distribution between the two countries' border. Even though several disease investigations have been conducted by many researchers, the disease epidemiology or transmission methods among people remained blurred and need to be further elucidated. In this paper, our aim is to provide a laconic review of common zoonotic diseases spread in Vietnam, outstanding cases and several factors predisposing to this alarming situation.

The possible zoonotic diseases transferring from pig to human in Vietnam.

Southeast Asia is considered one of worldwide hotspots consisting many distinct zoonotic infections. With optimal condition for the development of various pathogens, Vietnam is facing serious risks of zoonotic diseases. Besides, more than 50% Vietnamese people settle in rustic areas and earn their livings through small-scale animal breeding. It is possible that zoonotic diseases can be easily spread to the population by close contact with the infected animals, their infected residues, contaminated water, soil, or other possible means of transmission. In fact, zoonotic infections-transmissible infections between vertebrate animals and humans-cover a wide range of diseases with distinctive clinical and epidemiological highlights. With insufficient understanding and swift alteration in toxicity of the pathogens, these infections have gained more concerns due to sophisticated routes of transmission and harmful threats to humans. Recently emerging viral diseases exerted potential dangers to human beings, which required many countries to impose immediate actions to prevent any complications. Vietnam has recorded several cases of zoonotic diseases, especially pig-related illnesses; however, the studies on these diseases in this country remain limited. This work aims to highlight the zoonotic diseases transferring from pigs to humans and discuss risk factors of these diseases in Vietnam.

The higher prevalence of developmental defects of enamel in the dioxin-affected region than non-dioxin-affected region: result from a cross-sectional study in Vietnam.

Developmental defects of enamel (DDE) are induced and regulated by several factors including genetics and the environment. There is evidence showing that dioxin in polluted areas has a strong effect on the health and development of teeth. However, there has been no study on DDE in the dioxin-affected regions in Vietnam. To identify the effect of dioxin on the prevalence of DDE in studied areas in Vietnam, a cross-sectional study was conducted in 2200 adults in the A Luoi district in the Thua Thien Hue province (the dioxin-affected region) and in the Kim Bang district in the Ha Nam province (dioxin-unaffected region) in 2015. All subjects were interviewed using a structured questionnaire and their teeth were examined and scored for enamel defects based on the 1992 FDI criteria. The defected teeth were then photographed. Our results showed that the DDE rate in A Luoi was 20.5% when measured as mouth prevalence and 5.8% when measured as tooth prevalence, while the rates in Kim Bang were 10.4 and 2.32% for mouth and tooth prevalence, respectively. Demarcated opacities were predominated in both districts (45.5% in A Luoi and 52.2% in Kim Bang). The DDE rate of the anterior teeth group was higher than that of the posterior teeth group. Most lesions presented on the buccal surface of the tooth. Overall, the DDE prevalence in the dioxin-affected region was 2.2 times higher than that in non-dioxin-affected region in the studied regions in Vietnam.

An Update on Anti-CD137 Antibodies in Immunotherapies for Cancer.

The selective expression of CD137 on cells of the immune system (e.g., T and DC cells) and oncogenic cells in several types of cancer leads this molecule to be an attractive target to discover cancer immunotherapy. Therefore, specific antibodies against CD137 are being studied and developed aiming to activate and enhance anti-cancer immune responses as well as suppress oncogenic cells. Accumulating evidence suggests that anti-CD137 antibodies can be used separately to prevent tumor in some cases, while in other cases, these antibodies need to be co-administered with other antibodies or drugs/vaccines/regents for a better performance. Thus, in this work, we aim to update and discuss current knowledge about anti-cancer effects of anti-CD137 antibodies as mono- and combined-immunotherapies.

Zika virus infection in Vietnam: current epidemic, strain origin, spreading risk, and perspective.

Zika virus infection and its associated microcephaly have being receiving global concern. This infection has spread widely since the first outbreak was recorded in Africa in 1952. Now, it has been reported in over 70 countries on five continents including Africa, North and South America, Asia, and Europe. Vietnam is one of the most recent countries which had cases of Zika virus infection at the end of 2016. This country has also reported the first case of a microcephaly-born baby which was probably linked to Zika virus infection. However, information on the Zika virus epidemic in Vietnam is still limited. This brief report intends to update the current Zika virus epidemic, and to discuss challenges and perspectives in controlling this infection in Vietnam.

Impact of antigen loading in tolerogenic nanoparticles to mitigate Th2-mediated allergic lung inflammation.

Allergic disease is a major global health concern that imposes significant life-altering and economic burdens on affected individuals. However, there is still no cure. Polymer-based nanoparticles (NP) have shown the potential to induce antigen (Ag)-specific immune tolerance in various Th1/17 and Th2-mediated immune disorders including autoimmunity and allergy. Common methods by which Ags are associated with NPs are through surface conjugation or encapsulation. However, these Ag delivery strategies can be associated with several caveats that dampen their effectiveness such as uncontrolled Ag loading, a high Ag burst release, and an increased immune recognition profile. We previously developed Ag-polymer conjugate NPs (acNPs) to overcome those noted limitations, while allowing for controlled delivery of precise quantities of Ag to innate immune cells for Ag-specific CD4 T cell modulation. Here, we utilized ovalbumin (OVA) protein-poly(lactic-co-glycolic acid) (PLGA) conjugate NPs (acNP-OVA) to elucidate the impact of Ag loading on the induction of Th2 tolerance using a prophylactic and therapeutic OVA/ALUM-induced mouse model of allergic lung inflammation (ALI) in comparison to Ag-encapsulated PLGA NPs (NP(Ag)). We demonstrate that acNP-OVA formulations reduced OVA-specific IgE and inhibited Th2 cytokine secretions in an Ag loading-dependent manner when administered prophylactically. Administration of acNP-OVA to pre-sensitized mice did not affect OVA-specific IgE and Th2 cytokines tended to be reduced, however, there was no clear Ag loading dependency. acNP-OVA with medium-to-low Ag loadings were well tolerated, while formulations with high Ag loadings, including NP(Ag) resulted in anaphylaxis. Overall, our results clarify the relationship between Ag loading and Ag-specific IgE and Th2 cytokine responses in a murine model of ALI, which provides insight useful for future design of tolerogenic NP-based immunotherapies.

Multimodal nanoparticle-containing modified suberoylanilide hydroxamic acid polymer conjugates to mitigate immune dysfunction in severe inflammation.

Excessive immune activation and immunosuppression are opposing factors that contribute to the dysregulated innate and adaptive immune responses seen in severe inflammation and sepsis. Here, a novel analog of the histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA-OH), was incorporated into immunomodulatory poly(lactic acid)-based nanoparticles (iNP-SAHA) by employing a prodrug approach through the covalent modification of poly(lactic-co-glycolic acid) (PLGA) with SAHA-OH. iNP-SAHA formulation allowed for controlled incorporation and delivery of SAHA-OH from iNP-SAHA and treatment led to multimodal biological responses including significant reductions in proinflammatory cytokine secretions and gene expression, while increasing the survival of primary macrophages under lipopolysaccharide (LPS) challenge. Using a lethal LPS-induced endotoxemia mouse model of sepsis, iNP-SAHA administration improved the survival of mice in a dose-dependent manner and tended to improve survival at the lowest doses compared to iNP control. Further, iNP-SAHA reduced the levels of plasma proinflammatory cytokines and chemokines associated with sepsis more significantly than iNP and similarly improved inflammation-induced spleen and liver toxicity as iNP, supporting its potential polypharmacological activity. Collectively, iNP-SAHA offers a potential drug delivery approach to modulate the multifaceted inflammatory responses observed in diseases such as sepsis.

Comparing the accuracy of two machine learning models in detection and classification of periapical lesions using periapical radiographs.

BACKGROUND: Previous deep learning-based studies were mainly conducted on detecting periapical lesions; limited information in classification, such as the periapical index (PAI) scoring system, is available. The study aimed to apply two deep learning models, Faster R-CNN and YOLOv4, in detecting and classifying periapical lesions using the PAI score from periapical radiographs (PR) in three different regions of the dental arch: anterior teeth, premolars, and molars. METHODS: Out of 2658 PR selected for the study, 2122 PR were used for training, 268 PR were used for validation and 268 PR were used for testing. The diagnosis made by experienced dentists was used as the reference diagnosis. RESULTS: The Faster R-CNN and YOLOv4 models obtained great sensitivity, specificity, accuracy, and precision for detecting periapical lesions. No clear difference in the performance of both models among these three regions was found. The true prediction of Faster R-CNN was 89%, 83.01% and 91.84% for PAI 3, PAI 4 and PAI 5 lesions, respectively. The corresponding values of YOLOv4 were 68.06%, 50.94%, and 65.31%. CONCLUSIONS: Our study demonstrated the potential of YOLOv4 and Faster R-CNN models for detecting and classifying periapical lesions based on the PAI scoring system using periapical radiographs.

A Dataset of apical periodontitis lesions in panoramic radiographs for deep-learning-based classification and detection.

Deep learning has been studied in recent years to identify periapical lesions- a significant indicator of periapical periodontitis in radiographs. An accurate dataset is essential for constructing an efficient learning model for detecting periapical lesions. In order to achieve this goal, we gathered and created a database of panoramic radiographs containing periapical lesions from the High-quality Dental Treatment Centre, School of Dentistry, Hanoi Medical University, between January 2016 and March 2021. Out of 16,519 radiographs, three experienced dentists identified 3,926 images of periapical lesions and annotated those lesions based on the Periapical Lesions Classification. By applying well-known data processing techniques (e.g. scaling, mirroring, and flipping), the amount of data is increased to 17,004 images through generating additional images for machine learning. The dataset has three folders: one for the original photos, one for the post-augmentation images, and the rest for the annotation of periapical lesions. The information could assist researchers in developing a predictive machine model for detecting periapical lesions in radiographs.

Lipid-Polymer Hybrid Nanoparticles Utilize B Cells and Dendritic Cells to Elicit Distinct Antigen-Specific CD4+ and CD8+ T Cell Responses.

Antigen-presenting cells (APCs) are widely studied for treating immune-mediated diseases, and dendritic cells (DCs) are potent APCs that uptake and present antigens (Ags). However, DCs face several challenges that hinder their clinical translation due to their inability to control Ag dosing and low abundance in peripheral blood. B cells are a potential alternative to DCs, but their poor nonspecific Ag uptake capabilities compromise controllable priming of T cells. Here, we developed phospholipid-conjugated Ags (L-Ags) and lipid-polymer hybrid nanoparticles (L/P-Ag NPs) as delivery platforms to expand the range of accessible APCs for use in T cell priming. These delivery platforms were evaluated using DCs, CD40-activated B cells, and resting B cells to understand the impacts of various Ag delivery mechanisms for generation of Ag-specific T cell responses. L-Ag delivery (termed depoting) of MHC class I- and II-restricted Ags successfully loaded all APC types in a tunable manner and primed both Ag-specific CD8+ and CD4+ T cells, respectively. Incorporating L-Ags and polymer-conjugated Ags (P-Ag) into NPs can direct Ags to different uptake pathways to engineer the dynamics of presentation and shape T cell responses. DCs were capable of processing and presenting Ag delivered from both L- and P-Ag NPs, yet B cells could only utilize Ag delivered from L-Ag NPs, which led to differential cytokine secretion profiles in coculture studies. Altogether, we show that L-Ags and P-Ags can be rationally paired within a single NP to leverage distinct delivery mechanisms to access multiple Ag processing pathways in two APC types, offering a modular delivery platform for engineering Ag-specific immunotherapies.

Excipient-Free Ionizable Polyester Nanoparticles for Lung-Selective and Innate Immune Cell Plasmid DNA and mRNA Transfection.

Extrahepatic nucleic acid delivery using polymers typically requires the synthesis and purification of custom monomers, post-synthetic modifications, and incorporation of additional excipients to augment their stability, endosomal escape, and in vivo effectiveness. Here, we report the development of a single-component and excipient-free, polyester-based nucleic acid delivery nanoparticle platform comprising ionizable N-methyldiethanolamine (MDET) and various hydrophobic alkyl diols (Cp) that achieves lung-selective nucleic acid transfection in vivo. PolyMDET and polyMDET-Cp polyplexes displayed high serum and enzymatic stability, while delivering pDNA or mRNA to "hard-to-transfect" innate immune cells. PolyMDET-C4 and polyMDET-C6 mediated high protein expression in lung alveolar macrophages and dendritic cells without inducing tissue damage or systemic inflammatory responses. Improved strategies using readily available starting materials to produce a simple, excipient-free, non-viral nucleic acid delivery platform with lung-selective and innate immune cell tropism has the potential to expedite clinical deployment of polymer-based genetic medicines.

Preformulation Studies with Phenylalanine Ammonia Lyase: Essential Prelude to a Microcapsule Formulation for the Management of Phenylketonuria.

Phenylalanine ammonia lyase (PAL) metabolizes phenylalanine to transcinnamic acid (TCA). Our eventual goal is to develop a PAL microcapsule formulation to deplete phenylalanine in the gastrointestinal tract (g.i.t). The focus of this research is pre-formulation studies with PAL. PAL exhibited undesirable time dependent decrease in activity due to TCA mediated product inhibition. Addition of bovine serum albumin (BSA) completely relieved product inhibition. Ultrafiltration experiments revealed that BSA acted by binding and sequestering TCA. PAL exhibits maximum activity at a pH of 8.5 and will need to be buffered to retain activity in the g.i.t. Buffer studies showed that a pH 8.5, 0.4 M Bicine buffer containing BSA was able to maintain maximal PAL activity against simulated gastric and intestinal fluid additions. Buffered PAL with BSA was able to rapidly and completely deplete phenylalanine in simulated mouse g.i.t conditions. A small fraction of phenylalanine in the g.i.t is present as dipeptides. Our studies established for the first time that PAL cannot metabolize phenylalanine dipeptides. Our results explain why previous trials with PAL in the management of phenylketonuria produced low efficacy. They will guide design of a PAL microcapsule formulation that maintains maximal PAL activity during its transit through the g.i.t.

Modified Suberoylanilide Hydroxamic Acid Reduced Drug-Associated Immune Cell Death and Organ Damage under Lipopolysaccharide Inflammatory Challenge.

Histone deacetylase inhibitors (HDACi) induce potent anti-inflammatory responses when used to treat inflammatory diseases. Suberoylanilide hydroxamic acid (SAHA), a pan-HDACi, decreases pro-inflammatory cytokine levels and attenuates cytokine storm in sepsis; however, its toxicity profile toward immune cells has limited its use as a sepsis therapeutic. Here, we developed a modification to SAHA by para-hydroxymethylating the capping group to generate SAHA-OH. We discovered that SAHA-OH provides a favorable improvement to the toxicity profile compared to SAHA. SAHA-OH significantly reduced primary macrophage apoptosis and splenic B cell death as well as mitigated organ damage using a lipopolysaccharide (LPS)-induced endotoxemia mouse model. Furthermore, SAHA-OH retained anti-inflammatory responses similar to SAHA as measured by reductions in LPS-induced proinflammatory cytokine secretions in vitro and in vivo. These effects were attributed to a decreased selectivity of HDAC1, 2, 3, 8 and an increased selectivity for HDAC6 for SAHA-OH as determined by IC50 values. Our results support the potential for SAHA-OH to modulate acute proinflammatory responses while mitigating SAHA-associated drug toxicity for use in the treatment of inflammation-associated diseases and conditions.

Microfluidic-Generated Immunomodulatory Nanoparticles and Formulation-Dependent Effects on Lipopolysaccharide-Induced Macrophage Inflammation.

Nanoparticles (NPs) have emerged as a highly useful and clinically translatable drug delivery platform for vast therapeutic payloads. Through the precise tuning of their physicochemical properties, NPs can be engineered to exhibit controlled drug release properties, enhanced circulation times, improved cellular uptake and targeting, and reduced toxicity profiles. Conventional bulk methods for the production of polymeric NPs suffer from the ability to control their size and polydispersity, batch-to-batch variability, significant preparation times, and low recovery. Here, we describe the development and optimization of a high-throughput microfluidic method to produce cargo-less immunomodulatory nanoparticles (iNPs) and their formulation-dependent anti-inflammatory properties for the modulation of lipopolysaccharide (LPS)-induced macrophage responses. Using poly(lactic acid) (PLA) as the core-forming polymer, a rapid and tunable microfluidic hydrodynamic flow-focusing method was developed and optimized to systematically evaluate the role of polymer and surfactant concentration, surfactant chemistry, and flow rate ratio (FRR) on the formation of iNPs. A set of iNPs with 6 different surface chemistries and 2 FRRs was then prepared to evaluate their inherent anti-inflammatory effects using bone marrow-derived macrophages stimulated with the Toll-like receptor 4 agonist, LPS. Finally, a lyophilization study was performed using various cryoprotectants and combinations to identify preferable conditions for iNP storage. Overall, we demonstrate a highly controlled and reproducible method for the formulation of iNPs using microfluidics and their formulation-dependent inherent anti-inflammatory immunomodulatory properties, which represents a potentially promising strategy for the management of inflammation.