A Review of Different Types of Liposomes and Their Advancements as a Form of Gene Therapy Treatment for Breast Cancer.

Breast cancer incidence and mortality rates have increased exponentially during the last decade, particularly among female patients. Current therapies, including surgery and chemotherapy, have significant negative physical and mental impacts on patients. As a safer alternative, gene therapy utilising a therapeutic gene with the potential to treat various ailments is being considered. Delivery of the gene generally utilises viral vectors. However, immunological reactions and even mortality have been recorded as side effects. As a result, non-viral vectors, such as liposomes, a system composed of lipid bilayers formed into nanoparticles, are being studied. Liposomes have demonstrated tremendous potential due to their limitless ability to combine many functions into a system with desirable characteristics and functionality. This article discusses cationic, anionic, and neutral liposomes with their stability, cytotoxicity, transfection ability, cellular uptake, and limitation as a gene carrier suitable for gene therapy specifically for cancer. Due to the more practical approach of employing electrostatic contact with the negatively charged nucleic acid and the cell membrane for absorption purposes, cationic liposomes appear to be more suited for formulation for gene delivery and therapy for breast cancer treatment. As the other alternatives have numerous complicated additional modifications, attachments need to be made to achieve a functional gene therapy system for breast cancer treatment, which were also discussed in this review. This review aimed to increase understanding and build a viable breast cancer gene therapy treatment strategy.

Porous Polymerized High Internal Phase Emulsions Prepared Using Proteins and Essential Oils for Antimicrobial Applications.

High internal phase emulsions (HIPEs) provide a versatile platform for encapsulating large volumes of therapeutics that are immiscible in water. A stable scaffold is obtained by polymerizing the external phase, resulting in polyHIPEs. However, fabrication of polyHIPEs usually requires using a considerable quantity of surfactants along with nonbiocompatible components, which hinders their biological applications, e.g., drug-eluting devices. We describe here a straightforward method for generating porous biomaterials by using proteins as both the emulsifier and the building blocks for the fabrication of polyHIPEs. We demonstrate the versatility of this method by using different essential oils as the internal phase. After the gelation of protein building blocks is triggered by the addition of reducing agents, a stable protein hydrogel containing essential oils can be formed. These oils can be either extracted to obtain protein-based porous scaffolds or slowly released for antimicrobial applications.

Lozenges with probiotic strains enhance oral immune response and health.

OBJECTIVE: Probiotics participate in regulating oral microbiota and reducing the prevalence of oral diseases; however, clinical research on probiotics is insufficient. Therefore, in this study, we performed in vitro screening of potential oral protective probiotic strains and then evaluated the clinical efficacy of the selected strains on maintaining oral health. MATERIALS AND METHODS: Fifty healthy individuals were recruited and randomly assigned into the placebo group and probiotics group, which included three strains of probiotics, Lactobacillus salivarius subs. salicinius AP-32, Lactobacillus paracasei ET-66, and Lactobacillus plantarum LPL28. Each group was blindly administered placebo or probiotics for four weeks. RESULTS: Next-generation sequencing results showed that the oral microbiota of Lactobacillus salivarius in the oral cavity were significantly increased in subjects supplemented with mixed probiotic lozenges. The anti-bacterial activities of viable probiotics were observed within two weeks. Both IgA levels and Lactobacillus and Bifidobacterium abundances in the oral cavity were significantly increased in the experimental groups, along with a reduced formation of plaque. Most participants reported that their oral health conditions and intestinal symptoms had improved. CONCLUSIONS: Overall, our clinical study suggests that oral probiotic lozenges may enhance oral immunity, modulate oral microbiota, and improve oral health.

Regulation of Proteins to the Cytosol Using Delivery Systems with Engineered Polymer Architecture.

Intracellular protein delivery enables selective regulation of cellular metabolism, signaling, and development through introduction of defined protein quantities into the cell. Most applications require that the delivered protein has access to the cytosol, either for protein activity or as a gateway to other organelles such as the nucleus. The vast majority of delivery vehicles employ an endosomal pathway however, and efficient release of entrapped protein cargo from the endosome remains a challenge. Recent research has made significant advances toward efficient cytosolic delivery of proteins using polymers, but the influence of polymer architecture on protein delivery is yet to be investigated. Here, we developed a family of dendronized polymers that enable systematic alterations of charge density and structure. We demonstrate that while modulation of surface functionality has a significant effect on overall delivery efficiency, the endosomal release rate can be highly regulated by manipulating polymer architecture. Notably, we show that large, multivalent structures cause slower sustained release, while rigid spherical structures result in rapid burst release.

Outcome of Chinese patients with hepatitis B at 96 weeks after functional cure with IFN versus combination regimens.

BACKGROUND & AIMS: Nucleotides with add-on interferon treatment (NUC-IFN) provide significantly higher rates of hepatitis B surface antigen (HBsAg) loss in patients with chronic hepatitis B (CHB). This study aimed to investigate the sustainability of HBsAg loss and the prevention of clinical relapse. METHODS: Patients with CHB who achieved HBsAg loss and HBV DNA levels <20 IU/ml after IFN or NUC-IFN therapy were enrolled and followed up for 96 weeks. The primary outcome was HBsAg negativity without viremia at week 96. Secondary outcomes included virological or clinical relapse and predictors of relapse. RESULTS: 420 patients were included in intention-to-treat analysis with 290 and 130 in the IFN and NUC-IFN groups respectively. At week 96, the intention-to-treat analysis revealed similar outcomes between groups, including HBsAg seroreversion (24.83% vs. 23.08%, P = .70), viremia (16.90% vs 13.08%, P = .32) and clinical relapse (11.38% vs 10.00%, P = .68); the per-protocol analyses also showed HBsAg seroreversion, viremia and clinical relapse in IFN group (15.50%, 6.59% and 0.39%) did not differ from those in NUC-IFN group (15.25%, 4.24% and 0.85%, P > .05). These outcomes were similar between patients who received entecavir and those who received telbivudine/lamivudine/adefovir before the combination therapy. In NUC-IFN-treated patients, fibrosis regression was observed at week 96. Baseline HBsAb negativity was independent predictors of HBsAg sero-reversion and recurrence of viremia in IFN treated group. CONCLUSION: NUC-IFN and IFN therapies are equally effective in achieving sustained functional cure and fibrosis regression. (ClinicalTrials.gov, Number NCT02336399).

Synchrotron X-Ray Analysis and Morphology Evidence for Stereo-Assemblies of Periodic Aggregates in Poly(3-hydroxybutyrate) with Unusual Photonic Iridescence.

3D morphology of poly(3-hydroxybutyrate) (PHB), crystallized in the presence of diluents of poly(1,3-trimethylene adipate) and poly(ethylene oxide), is probed using a novel approach coupled with selective etching. For interpreting the mechanisms of crystal periodic aggregation, various microscopic techniques and synchrotron microbeam X-ray analysis are used to observe the top surface in connection with the 3D crystal assemblies. Periodic grating architectures, with the cross-bar pitch exactly matching with the optical band spacing, are proved in banded PHB. The crystals under the ridge branch out to spawn finer crystals orienting/bending horizontally underneath the valley band, repeating till species drainage or impingement. The grating structure in the banded PHB resembles many nature's iridescence crystals and is further proved by photonic reflection results as a critical breakthrough novel finding.

Direct Cytosolic Delivery of Proteins through Coengineering of Proteins and Polymeric Delivery Vehicles.

Nanocarrier-mediated protein delivery is a promising strategy for fundamental research and therapeutic applications. However, the efficacy of the current platforms for delivery into cells is limited by endosomal entrapment of delivered protein cargo with concomitantly inefficient access to the cytosol and other organelles, including the nucleus. We report here a robust, versatile polymeric-protein nanocomposite (PPNC) platform capable of efficient (≥90%) delivery of proteins to the cytosol. We synthesized a library of guanidinium-functionalized poly(oxanorborneneimide) (PONI) homopolymers with varying molecular weights to stabilize and deliver engineered proteins featuring terminal oligoglutamate "E-tags". The polymers were screened for cytosolic delivery efficiency using imaging flow cytometry with cytosolic delivery validated using confocal microscopy and activity of the delivered proteins demonstrated through functional assays. These studies indicate that the PPNC platform provides highly effective and tunable cytosolic delivery over a wide range of formulations, making them robust agents for therapeutic protein delivery.

Oral P. gingivalis impairs gut permeability and mediates immune responses associated with neurodegeneration in LRRK2 R1441G mice.

BACKGROUND: The R1441G mutation in the leucine-rich repeat kinase 2 (LRRK2) gene results in late-onset Parkinson's disease (PD). Peripheral inflammation and gut microbiota are closely associated with the pathogenesis of PD. Chronic periodontitis is a common type of peripheral inflammation, which is associated with PD. Porphyromonas gingivalis (Pg), the most common bacterium causing chronic periodontitis, can cause alteration of gut microbiota. It is not known whether Pg-induced dysbiosis plays a role in the pathophysiology of PD. METHODS: In this study, live Pg were orally administrated to animals, three times a week for 1 month. Pg-derived lipopolysaccharide (LPS) was used to stimulate mononuclear cells in vitro. The effects of oral Pg administration on the gut and brain were evaluated through behaviors, morphology, and cytokine expression. RESULTS: Dopaminergic neurons in the substantia nigra were reduced, and activated microglial cells were increased in R1441G mice given oral Pg. In addition, an increase in mRNA expression of tumor necrosis factor (TNF-α) and interleukin-1ß (IL-1ß) as well as protein level of α-synuclein together with a decrease in zonula occludens-1 (Zo-1) was detected in the colon in Pg-treated R1441G mice. Furthermore, serum interleukin-17A (IL-17A) and brain IL-17 receptor A (IL-17RA) were increased in Pg-treated R1441G mice. CONCLUSIONS: These findings suggest that oral Pg-induced inflammation may play an important role in the pathophysiology of LRRK2-associated PD.

Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery.

Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

Molecular Detection and Genotyping of Toxoplasma gondii in Edward's Long-Tailed Rats (Leopoldamys edwardsi).

Toxoplasma gondii is an important zoonotic parasite infecting humans and various animals with a worldwide distribution. However, limited information is available on T. gondii infection in wild rats. The present study aimed to examine the prevalence and characterize the genotypes of T. gondii in wild rats in two regions of China. Brain tissues were collected from 111 Edward's long-tailed rats (Leopoldamys edwardsi) and 117 Bower's white-toothed rats (Berylmys bowersi) between November 2017 and January 2018. Genomic DNA was extracted and amplified by PCR targeting the T. gondii B1 gene. B1 gene-positive samples were genotyped at 10 genetic markers (SAG1, SAG2 [5', 3'] and [alternative], SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico) using multilocus nested polymerase chain reaction/restriction fragment length polymorphism. Six (5.41%, 6/111) Edward's long-tailed rats from Chongqing Municipality were positive for T. gondii B1 gene, whereas no T. gondii infection was detected in Bower's white-toothed rats (n = 117) from Guangdong province. T. gondii prevalence in female and male rats was 1.77% (2/113) and 3.48 (4/115), respectively. Four of the six positive DNA samples were completely genotyped at 10 genetic loci and were identified as ToxoDB#20. The present study revealed the occurrence of T. gondii infection in Edward's long-tailed rats. These findings raised public health concerning about T. gondii infection in wild rats. These results provide reference data for understanding the distribution of T. gondii genotypes in wild rats in China.

Engineered Polymer Nanoparticles with Unprecedented Antimicrobial Efficacy and Therapeutic Indices against Multidrug-Resistant Bacteria and Biofilms.

The rapid emergence of antibiotic-resistant bacterial "superbugs" with concomitant treatment failure and high mortality rates presents a severe threat to global health. The superbug risk is further exacerbated by chronic infections generated from antibiotic-resistant biofilms that render them refractory to available treatments. We hypothesized that efficient antimicrobial agents could be generated through careful engineering of hydrophobic and cationic domains in a synthetic semirigid polymer scaffold, mirroring and amplifying attributes of antimicrobial peptides. We report the creation of polymeric nanoparticles with highly efficient antimicrobial properties. These nanoparticles eradicate biofilms with low toxicity to mammalian cells and feature unprecedented therapeutic indices against red blood cells. Most notably, bacterial resistance toward these nanoparticles was not observed after 20 serial passages, in stark contrast to clinically relevant antibiotics where significant resistance occurred after only a few passages.

Biodegradable Nanocomposite Antimicrobials for the Eradication of Multidrug-Resistant Bacterial Biofilms without Accumulated Resistance.

Infections caused by multidrug-resistant (MDR) bacteria are a rapidly growing threat to human health, in many cases exacerbated by their presence in biofilms. We report here a biocompatible oil-in-water cross-linked polymeric nanocomposite that degrades in the presence of physiologically relevant biomolecules. These degradable nanocomposites demonstrated broad-spectrum penetration and elimination of MDR bacteria, eliminating biofilms with no toxicity to cocultured mammalian fibroblast cells. Notably, serial passaging revealed that bacteria were unable to develop resistance toward these nanocomposites, highlighting the therapeutic promise of this platform.

Polymer-free versus permanent polymer-coated drug eluting stents for the treatment of coronary artery disease: A meta-analysis of randomized trials.

BACKGROUND: Polymer-free drug eluting stents (PF-DES) were developed, in part, to overcome risk of late ischemic events observed with permanent polymer-coated DES (PP-DES). However, trial results are inconsistent with longer-term safety and efficacy of PF-DES remaining unknown. We performed a meta-analysis of randomized trials assessing outcomes of patients receiving PF-DES versus PP-DES for treatment of coronary artery disease (CAD). METHODS: Electronic searches were performed for randomized trials comparing outcomes between PF-DES and PP-DES. Trials reporting major adverse cardiovascular events (MACE), myocardial infarction (MI), stent thrombosis (ST), all-cause death, target lesion/vessel revascularization (TLR/TVR), and late lumen loss (LLL) were included. Analyses were performed at longest follow-up and landmarked beyond 1-year. RESULTS: Twelve trials (6,943 patients) were included. There was no significant difference in MACE between PF-DES and PP-DES at longest follow-up (Odds Ratio [OR] 0.96, 95%CI 0.85-1.10, P = 0.59) or landmark analysis beyond 1-year (OR 0.96, 95%CI 0.76-1.20, P = 0.70). Although PF-DES were associated with a significant reduction in all-cause death (OR 0.85, 95%CI 0.72-1.00, P < 0.05), this effect was not present on landmark analysis beyond 1-year (OR 0.89, 95%CI 0.73-1.10, P = 0.30). There were no differences observed for MI (OR 1.00, 95%CI 0.77-1.28, P = 0.99) or ST (OR 0.95, 95%CI 0.54-1.68, P = 0.86), with similar efficacy outcomes including TVR (OR 1.07, 95%CI 0.91-1.26, P = 0.42), TLR (OR 1.03, 95%CI 0.88-1.21, P = 0.68) and angiographic LLL (pooled mean difference 0.01 mm, 95%CI -0.08 to 0.11, P = 0.76). CONCLUSIONS: PF-DES are as safe and efficacious as PP-DES for the treatment of patients with CAD, but do not significantly reduce late ischemic complications.

Double-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable capillary electrophoresis and capillary electrophoresis with mass spectrometry glycan analysis.

Glycosylation plays an important role in protein conformations and functions as well as many biological activities. Capillary electrophoresis combined with various detection methods provided remarkable developments for high-sensitivity glycan profiling. The coating of the capillary is needed for highly polar molecules from complex biosamples. A poly(vinyl alcohol)-coated capillary is commonly utilized in the capillary electrophoresis separation of saccharides sample due to the high-hydrophilicity properties. A modified facile coating workflow was carried out to acquire a novel multiple-layer poly(vinyl alcohol)-coated capillary for highly sensitive and stable analysis of glycans. The migration time fluctuation was used as index in the optimization of layers and a double layer was finally chosen, considering both the effects and simplicity in fabrication. With migration time relative standard deviation less than 1% and theoretical plates kept stable during 100 consecutive separations, the method was presented to be suitable for the analysis of glycosylation with wide linear dynamic range and good reproducibility. The glycan profiling of enzymatically released N-glycans from human serum was obtained by the presented capillary electrophoresis method combined with mass spectrometry detection with acceptable results.

Western blotting by thin-film direct coating.

A novel thin-film direct coating (TDC) technique was developed to markedly reduce the amount of antibody required for Western blotting (WB). Automatic application of the technique for a few seconds easily and homogeneously coats the specific primary antibody on the polyvinylidene fluoride (PVDF) membrane. While conventional WB requires 0.4 µg of the primary antibody, the proposed technique only uses 4 × 10(-2) µg, which can be reduced further to 4 × 10(-5) µg by reducing the coater width. Moreover, the proposed process reduces antibody probing times from 60 to 10 min. The quantification capability of TDC WB showed high linearity within a 4-log2 dynamic range for detecting target antigen glutathione-S-transferase. Furthermore, TDC WB can specifically detect the extrinsic glutathione-S-transferase added in the Escherichia coli or 293T cell lysate with better staining sensitivity than conventional WB. TDC WB can also clearly probe the intrinsic ß-actin, α-tubulin, and glyceraldehyde 3-phosphate dehydrogenase, which are usually used as control proteins in biological experiments. This novel technique has been shown to not only have valuable potential for increasing WB efficiency but also for providing significant material savings for future biomedical applications.

A modified technique to improve the outcome of intubation with a left-sided double-lumen endobronchial tube.

BACKGROUND: The use of a video-assisted laryngoscope (VL) has been shown to reduce the time to achieve intubation with a double-lumen endobronchial tube (DLT). As the blade of the VL is curved differently to a standard laryngoscope, the DLT must be angled into a hockey stick shape to fit properly. We conducted a study to establish which direction of angulation was best to facilitate correct positioning of the DLT when using a VL. METHODS: We enrolled patients scheduled for thoracic surgery who required intubation with a DLT. They were prospectively randomized into one of two groups: those intubated with a DLT angled to conceal the tracheal orifice (the tracheal orifice-covered, TOC) group or the tracheal orifice-exposed (TOE) group. The composite primary outcome measures were time taken to intubate and the frequency of first-time success. The time taken to intubate was divided into: T1, the time from mouth opening to visualization of the vocal cords with the VL; and T2, the time taken to advance the DLT through the cords until its tip lay within the trachea and three carbon dioxide waveforms had been detected by capnography. The hemodynamic responses to intubation and intubation-related adverse events were also recorded. RESULTS: Sixty-six patients completed the study, with 33 in each group. Total intubation time was significantly shorter in the TOC group (mean 30.6 ± standard deviation 2.7 seconds versus 38.7 ± 3.3 seconds, p <0.0001). T2 was also significantly shorter in the TOC group than the TOE group (27.2 ± 2.5 seconds versus 34.9 ± 3.0 seconds, p <0.0001). The severity of hoarseness on the first postoperative day and sore throat on the fourth postoperative day were significantly lower in the TOC group than the TOE group (p = 0.02 and <0.0001, respectively). The hemodynamic responses to intubation were broadly similar between the groups. CONCLUSION: When placing a left-sided DLT using a VL, angling the bronchial lumen to a hockey stick shape that conceals the tracheal lumen saves time and ameliorates the severity of post-intubation complications. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01605591.

Systemic Immune-Inflammation Index and Systemic Inflammation Response Index are Associated With Periodontitis: Evidence From NHANES 2009 to 2014.

INTRODUCTION AND AIMS: Periodontitis, a chronic inflammatory condition affecting the supporting structures of the teeth, is a substantial public health burrden whilst impacting the life quality of those affected. Elevated levels of systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) have been implicated in various inflammatory conditions. This study aimed to investigate the relationship between SII and SIRI with periodontitis. METHODS: The study examined a total of 8666 participants in the 2009 to 2014 National Health and Nutrition Examination Survey (NHANES). The study compared the weighted prevalence of periodontitis among various groups. The association between SII, SIRI levels, and periodontitis was analyzed using binary logistic regression. Additionally, we explored nonlinear relationships between SII, SIRI, and the prevalence of periodontitis using restricted cubic spline (RCS) plots. RESULTS: Among participants in the fourth quartile (Q4) of SII and SIRI, the highest prevalence of periodontitis was observed, with rates of 44.87% and 48.41%, respectively. After adjusting for all covariates, the odds ratio (OR) for periodontitis associated with SII Q4 was 1.19 (95% CI 1.02, 1.39, P = .03), while for SIRI Q4, it was 1.18 (95% CI 1.01, 1.39, P = .04). In addition, the results of sensitivity analysis revealed consistent findings, indicating that after adjusting for all covariates, the OR for periodontitis associated with SII Q4 and SIRI Q4 remained statistically significant. Specifically, the OR for periodontitis associated with SII Q4 was 1.19 (95% CI 1.02, 1.39, P = .03), while for SIRI Q4, it was 1.19 (95% CI 1.01, 1.40, P = .04). CONCLUSIONS: These results indicate that elevated SII and SIRI levels are associated with an increased prevalence of periodontitis. CLINICAL RELEVANCE: These findings suggest a potential connection between systemic inflammation and periodontitis, highlighting the importance of periodontitis patients being aware of their systemic diseases that are inflammatory in nature such as chronic cardiovascular afflictions.

An outer membrane vesicle specific lipoprotein promotes Porphyromonas gingivalis aggregation on red blood cells.

Porphyromonas gingivalis uses a variety of mechanisms to actively interact with and promote the hydrolysis of red blood cells (RBCs) to obtain iron in the form of heme. In this study, we investigated the function of lipoprotein PG1881 which was previously shown to be up-regulated during subsurface growth and selectively enriched on outer membrane vesicles (OMVs). Our results show that wildtype strain W83 formed large aggregates encompassing RBCs whereas the PG1881 deletion mutant remained predominately as individual cells. Using a PG1881 antibody, immunofluorescence revealed that the wildtype strain's aggregation to RBCs involves an extracellular matrix enriched with PG1881. Our findings discover that RBCs elicit cell aggregation and matrix formation by P. gingivalis and that this process is promoted by an OMV-specific lipoprotein. We propose this strategy is advantageous for nutrient acquisition as well as dissemination from the oral cavity and survival of this periodontal pathogen.

Efficacy of therapeutic play for pediatric brain tumor patients during external beam radiotherapy.

OBJECTIVE: External beam radiotherapy (EBRT) is frequently used to improve disease control for pediatric brain tumor patients. However, to facilitate the radiotherapy (RT) procedure, "forced" type interventions including conscious sedation or general anesthesia are frequently used to manage patients' fear and anxiety. The aim of this study was to investigate the effects of therapeutic play (TP) in reducing anxiety for pediatric brain tumor patients treated by EBRT. METHODS: Between April 1st and September 30th, 2009, 19 young brain tumor patients, aged 3-15 years and recommended for RT, were recruited: ten to a control group and nine to the study intervention group. The study group was introduced with TP during EBRT. The Beck Youth Anxiety Inventory and the Faces Anxiety Scale were used to evaluate patients' psychological levels of anxiety. The heart rate variability and salivary cortisol concentrations were used to indicate the patients' physical levels of anxiety. Both the psychological and physiological tests were administered to all subjects before and after the RT procedure. RESULTS: The study group had significantly lower anxiety scores and expressed fewer negative emotions than did the control group before EBRT. CONCLUSIONS: TP can not only improve the quality of medical services but can also reduce costs and staffing demands. In addition, it can help lower young patients' anxiety and fear during medical procedures. As a result, it further decreases the potential negative impacts of hospitalization on these young patients.

Dental scaling and lower risk of spontaneous intracranial hemorrhage.

Background: -Spontaneous intracranial hemorrhage (ICH) has high fatality while has few proven treatments. We aim at investigating the association between dental scaling (DS) and the risk of ICH. Methods: -In this cohort study, two cohorts were matched by propensity score based on potential confounders. Data from ICH between January 2008 and December 2014 in Taiwan were analyzed. The subjects underwent DS at least 6 times between January 1, 2002, and December 31, 2007, while the matched controls did not undergo any DS during the same period. Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing confounders. Results: -Each cohort consisted of 681,126 subjects. Compared with the non-DS cohort, the regular-DS cohort had a significantly lower incidence of ICH (0.8% vs 1.2%; P < 0.0001), and the adjusted hazards ratio (aHR) of 7-year ICH was 0.61 (95% confidence interval, CI, 0.59-0.63; P < 0.0001). The 30-39-year age group of the regular-DS cohort had the lowest HR (0.57; 95% CI, 0.52-0.61; P < 0.0001) of 7-year ICH when compared with similar controls. Compared with the controls, the regular-DS cohort also had significantly lower HR (0.82; 95% CI, 0.81-0.82; P < 0.0001) of 7-year hypertension. Compared with those without DS, the lowest risk of intracerebral hemorrhage was observed in the male participants with regular DS (0.43; 95% CI, 0.40-0.47; P < 0.0001). Conclusions: -Regular DS was consistently associated with lower ICH risk in subjects aged 30-59 years, which may benefit from the decreased HBP risk. DS had a potential role in the prophylaxis for ICH, a condition with a high disability or mortality.