Antimicrobial and Antifouling Effects of Petal-Like Nanostructure by Evaporation-Induced Self-Assembly for Personal Protective Equipment.

Although the personal protective equipment (PPE) used by healthcare workers (HCWs) effectively blocks hazardous substances and pathogens, it does not fully rule out the possibility of infection, as pathogens surviving on the fabric surface pose a substantial risk of cross-infection through unintended means. Therefore, PPE materials that exhibit effective biocidal activity while minimizing contamination by viscous body fluids (e.g., blood and saliva) and pathogen-laden droplets are highly sought. In this study, petal-like nanostructures (PNSs) are synthesized through the vertical rearrangement of colloidal lamellar bilayers via evaporation-induced self-assembly of octadecylamine, silica-alumina sol, and diverse photosensitizer. The developed method is compatible with various fabrics and imparts visible-light-activated antimicrobial and superhydrophobic-based antifouling activities. PNS-coated fabrics could provide a high level of protection and effectively block pathogen transmission as exemplified by their ability to roll off viscous body fluids reducing bacterial droplet adhesion and to inactivate various microorganisms. The combination of antifouling and photobiocidal activities results in the complete inactivation of sprayed pathogen-laden droplets within 30 min. Thus, this study paves the way for effective contagious disease management and the protection of HCWs in general medical environments, inspiring further research on the fabrication of materials that integrate multiple useful functionalities.

Photochemical Consideration in the Interactions between Blood Proteins and Layered Inorganic Materials.

Interactions between layered double hydroxide (LDH) nanomaterials and plasma proteins according to their particle size and surface charge were evaluated. The LDHs with different particle size (150, 350 and 2000 nm) were prepared by adjusting hydrothermal treatment and urea hydrolysis and subsequent organic coating with citrate, malite and serite was applied to control the surface charge (ζ-potential: -15, 6 and 36 mV). Adsorption isotherms and Stern-Volmer plots for fluorescence quenching indicated that the human blood plasma had weak interactions toward all the types of LDHs. The adsorption isotherms did not show significant differences in the size and surface charges, while the fluorescence quenching ratio increased with the increase in the surface charge, implying that electrostatic interaction played a major role in their interactions. The fluorescence quenching of three types of plasma proteins (human serum albumin, γ-globulin and fibrinogen) by the surface charge-controlled LDHs suggested that the proteins adsorbed on the LDHs with a single layer and additional proteins were weakly adsorbed to surround the LDHs with adsorbed proteins. It was concluded that the LDH nanomaterials are fairly compatible for blood components due to the protein corona while the electrostatic interaction can affect their interaction with the proteins.

Blood Compatibility of Drug-Inorganic Hybrid in Human Blood: Red Blood Cell Hitchhiking and Soft Protein Corona.

A drug-delivery system consisting of an inorganic host-layered double hydroxide (LDH)-and an anticancer drug-methotrexate (MTX)-was prepared via the intercalation route (MTX-LDH), and its hematocompatibility was investigated. Hemolysis, a red blood cell counting assay, and optical microscopy revealed that the MTX-LDH had no harmful toxic effect on blood cells. Both scanning electron microscopy and atomic force microscopy exhibited that the MTX-LDH particles softly landed on the concave part inred blood cells without serious morphological changes of the cells. The time-dependent change in the surface charge and hydrodynamic radius of MTX-LDH in the plasma condition demonstrated that the proteins can be gently adsorbed on the MTX-LDH particles, possibly through protein corona, giving rise to good colloidal stability. The fluorescence quenching assay was carried out to monitor the interaction between MTX-LDH and plasma protein, and the result showed that the MTX-LDH had less dynamic interaction with protein compared with MTX alone, due to the capsule moiety of the LDH host. It was verified by a quartz crystal microbalance assay that the surface interaction between MTX-LDH and protein was reversible and reproducible, and the type of protein corona was a soft one, having flexibility toward the biological environment.

Hyaluronic acid-coated gold nanoparticles as a controlled drug delivery system for poorly water-soluble drugs.

Hyaluronic acid (HA) is a natural linear polysaccharide which has been widely used in cosmetics and pharmaceuticals including drug delivery systems because of its excellent biocompatibility. In this study, we investigated the one-pot synthesis of HA-coated gold nanoparticles (AuNP-HA) as a drug delivery carrier. The HAs with different molecular weights were produced by e-beam irradiation and employed as coating materials for AuNPs. Sulfasalazine (SSZ), a poorly water-soluble drug, was used to demonstrate the efficiency of drug delivery and the controlled release behaviour of the AuNP-HA. As the molecular weight of the HA decreased, the drug encapsulation efficiency of the SSZ increased up to 94%, while drug loading capacity of the SSZ was maintained at the level of about 70%. The prepared AuNP-HA-SSZ exhibited slow release of the SSZ over a short time and excellent sensitivity to different pHs and physiological conditions. The SSZ release rate was the lowest in simulated gastric conditions and the highest in simulated intestinal conditions. In this case, the AuNP-HA protects the SSZ from release under the acidic pH conditions in the stomach; on the other hand, the drug release was facilitated in the basic environment of the small intestine and colon. The SSZ was released under simulated intestinal conditions through anomalous drug transport and followed the Korsmeyer-Peppas model. Therefore, this study suggests that AuNP-HA is a promising orally-administered and intestine-targeted drug delivery system with controlled release characteristics.

A claudin-9-based ion permeability barrier is essential for hearing.

Hereditary hearing loss is one of the most common birth defects, yet the majority of genes required for audition is thought to remain unidentified. Ethylnitrosourea (ENU)-mutagenesis has been a valuable approach for generating new animal models of deafness and discovering previously unrecognized gene functions. Here we report on the characterization of a new ENU-induced mouse mutant (nmf329) that exhibits recessively inherited deafness. We found a widespread loss of sensory hair cells in the hearing organs of nmf329 mice after the second week of life. Positional cloning revealed that the nmf329 strain carries a missense mutation in the claudin-9 gene, which encodes a tight junction protein with unknown biological function. In an epithelial cell line, heterologous expression of wild-type claudin-9 reduced the paracellular permeability to Na+ and K+, and the nmf329 mutation eliminated this ion barrier function without affecting the plasma membrane localization of claudin-9. In the nmf329 mouse line, the perilymphatic K+ concentration was found to be elevated, suggesting that the cochlear tight junctions were dysfunctional. Furthermore, the hair-cell loss in the claudin-9-defective cochlea was rescued in vitro when the explanted hearing organs were cultured in a low-K+ milieu and in vivo when the endocochlear K+-driving force was diminished by deletion of the pou3f4 gene. Overall, our data indicate that claudin-9 is required for the preservation of sensory cells in the hearing organ because claudin-9-defective tight junctions fail to shield the basolateral side of hair cells from the K+-rich endolymph. In the tight-junction complexes of hair cells, claudin-9 is localized specifically to a subdomain that is underneath more apical tight-junction strands formed by other claudins. Thus, the analysis of claudin-9 mutant mice suggests that even the deeper (subapical) tight-junction strands have biologically important ion barrier function.

Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System.

A layered double hydroxide (LDH)-based anticancer delivery system was investigated in terms of crystalline phase, particle size, hydrodynamic radius, zeta potential, etc. through in vitro and in vivo study. Size controlled LDH with anticancer drug methotrexate (MTX) incorporation was successfully prepared through step-by-step hydrothermal reaction and ion-exchange reaction. The MTX-LDH was determined to have a neutral surface charge and strong agglomeration in the neutral aqueous condition due to the surface adsorbed MTX; however, the existence of proteins in the media dramatically reduced agglomeration, resulting in the hydrodynamic radius of MTX-LDH being similar to the primary particle size. The protein fluorescence quenching assay exhibited that MTX readily reduced the fluorescence of proteins, suggesting that the interaction between MTX and proteins was strong. On the other hand, MTX-LDH showed much less binding constant to proteins compared with MTX, implying that the protein interaction of MTX was effectively blocked by the LDH carrier. The in vivo hemolysis assay after intravenous injection of MTX-LDH showed neither significant reduction in red blood cell number nor membrane damage. Furthermore, the morphology of red blood cells in a mouse model did not change upon MTX-LDH injection. Scanning electron microscopy showed that the MTX-LDH particles were attached on the blood cells without serious denaturation of cellular morphology, taking advantage of the cell hitchhiking property.

Determination of the fate and biological responses of food additive silica particles in commercial foods.

Synthetic amorphous silica (SAS) is widely added to commercial foods as an anticaking agent. Concern about the potential application of nanosized silica in foods has increased as nanomaterials are not intended for use as food additives. This study evaluated the particle size distributions and biological responses of food additive SAS. An accurate, sensitive, and cost-effective analytical method for probing SAS was established, and quantitative analysis of its presence in commercial foods was performed. The results demonstrate that food additive SAS is an aggregated material composed of nanosized particles with nanosized aggregates of silica particles identified in commercial foods. Food additive SAS did not exhibit acute cytotoxicity compared to both general-grade nano (G-nano) and bulk (G-bulk) silica. Moreover, intestinal transport amounts of food additive SAS were significantly lower than for G-nano. Taken together, we find that food additive SAS does not exhibit acute toxicity resulting from nanosized materials.

Developmental delays consistent with cochlear hypothyroidism contribute to failure to develop hearing in mice lacking Slc26a4/pendrin expression.

Mutations of SLC26A4 cause an enlarged vestibular aqueduct, nonsyndromic deafness, and deafness as part of Pendred syndrome. SLC26A4 encodes pendrin, an anion exchanger located in the cochlea, thyroid, and kidney. The goal of the present study was to determine whether developmental delays, possibly mediated by systemic or local hypothyroidism, contribute to the failure to develop hearing in mice lacking Slc26a4 (Slc26a4(-/-)). We evaluated thyroid function by voltage and pH measurements, by array-assisted gene expression analysis, and by determination of plasma thyroxine levels. Cochlear development was evaluated for signs of hypothyroidism by microscopy, in situ hybridization, and quantitative RT-PCR. No differences in plasma thyroxine levels were found in Slc26a4(-/-) and sex-matched Slc26a4(+/-) littermates between postnatal day 5 (P5) and P90. In adult Slc26a4(-/-) mice, the transepithelial potential and the pH of thyroid follicles were reduced. No differences in the expression of genes that participate in thyroid hormone synthesis or ion transport were observed at P15, when plasma thyroxine levels peaked. Scala media of the cochlea was 10-fold enlarged, bulging into and thereby displacing fibrocytes, which express Dio2 to generate a cochlear thyroid hormone peak at P7. Cochlear development, including tunnel opening, arrival of efferent innervation at outer hair cells, endochondral and intramembraneous ossification, and developmental changes in the expression of Dio2, Dio3, and Tectb were delayed by 1-4 days. These data suggest that pendrin functions as a HCO3- transporter in the thyroid, that Slc26a4(-/-) mice are systemically euthyroid, and that delays in cochlear development, possibly due to local hypothyroidism, lead to the failure to develop hearing.

Food Additive Titanium Dioxide and Its Fate in Commercial Foods.

Titanium dioxide (TiO2) is one of the most extensively utilized food additives (E171) in the food industry. Along with nanotechnology development, the concern about the presence of nanostructured particles in E171 TiO2 and commercial food products is growing. In the present study, the physicochemical properties of commercially available E171 TiO2 particles, including particle size distribution, were investigated, followed by their cytotoxicity and intestinal transport evaluation. The fate determination and quantification of E171 TiO2 in commercial foods were carried out based on the analytical procedure developed using simulated foods. The results demonstrated that TiO2 is a material mainly composed of particles larger than 100 nm, but present as an agglomerated or aggregated particle in commercial foods with amounts of less than 1% (wt/wt). Titanium dioxide particles generated reactive oxygen species and inhibited long-term colony formation, but the cytotoxicity was not related to particle size distribution or particle type (food- or general-grade). All TiO2 particles were mainly transported by microfold (M) cells, but also by intestinal tight junction. These findings will be useful for TiO2 application in the food industry and predicting its potential toxicity.

Endaural Laser-Assisted Single-Stage Inside-Out Cholesteatoma Surgery (LASIC) to Treat Advanced Congenital Cholesteatoma.

OBJECTIVES: Investigation of endaural laser-assisted single-stage inside-out cholesteatoma surgery (LASIC) to treat advanced congenital cholesteatoma (ACC) by a modified staging system based on ossicle status. STUDY DESIGN: A retrospective case review. SETTING: A university hospital otology referral clinic. PATIENTS: Two hundred consecutive pediatric patients with ACC were enrolled. INTERVENTIONS: Endaural LASIC and postoperative temporal bone computed tomography (CT). MAIN OUTCOME MEASURES: Residual or recurrent CC and audiological outcomes. RESULTS: LASIC was feasible in 98.0% of patients. Single-stage ossiculoplasty was performed in 95.5% of patients. Hearing preservation to less than 20 dB was 59.2% and to the preoperative hearing level was 84.5%. Mastoid invasion did not result in worse recidivism or hearing loss (HL) but further invasion of the stapes superstructure (stage IV) significantly elevated both the recidivism (16.7%) and the risk for HL (to 84.8%) (p = 0.001). Ossicle preservation LASIC was frequently possible in stage III posterior type (75.6%), whereas it was rarely possibly (15.4%) in the anterior type. Incudostapedial joint (ISJ) invasion in the absence of cochleariform process (CP) invasion (III-posterior) did not increase the incidence of HL (6.1%) or recidivism (2.4%). However, simultaneous invasion of the CP and ISJ (III-anterior) elevated the risk of HL by 46.2% by ossicle removal, although recidivism was not increased (3.8%). CONCLUSIONS: Endaural LASIC for ACC achieved satisfactory recidivism (overall 7.5%, 16.7% in stage IV) comparable to early CC (17.2%). An ossicle status-based staging system was more efficient for correlation with audiologic and surgical outcomes of CC than that of mastoid invasion.

Bilateral simultaneous facial nerve palsy: clinical analysis in seven cases.

OBJECTIVE: To analyze clinical manifestations and prognosis of bilateral simultaneous facial nerve palsy (BS-FNP). STUDY DESIGN: : Retrospective case review with current follow-up wherever possible. SETTING: : Tertiary referral centers. PATIENTS: Patients (n = 7; 4 women and 3 men; mean age, 37 yr; range, 18-58 yr) diagnosed with BS-FNP at the time of their first visit. INTERVENTION: Therapy with systemic corticosteroids and antiviral agents and outpatient follow-up for 1 month to 4 years after discharge. MAIN OUTCOME MEASURE: Assessment of recovery from FNP using the House-Brackmann grading system. RESULTS: : The occurrence rate of BS-FNP of total FNP cases for the past 10 years was 0.4%. All patients showed palsy more severe than House-Brackmann Grade IV and similar grades of FNP bilaterally. Patients complained of the involvement of the other side within 1 to 6 days of the involvement of 1 side (mean period, 3.4 d). Bell's palsy was the most common cause (5 of 7; 71.4%), the other 2 being infectious mononucleosis and Ramsay Hunt syndrome zoster sine herpete (1 of 7; 14.3% each). Although most patients recovered completely within 1 to 6 months, 1 with a positive Varicella zoster virus immunoglobulin M titer showed bilateral House-Brackmann Grade II FNP after recovery. No recurrence was noted during the follow-up period. CONCLUSION: Bell's palsy is the most common cause of BS-FNP in authors' centers. Although BS-FNP may show more severe paralysis, the overall prognosis in most cases is as good as that in unilateral FNP, excluding life-threatening or traumatic cases. Differential diagnosis is very important because the treatment outcome of BS-FNP depends on the cause.

Management of complications in cochlear implantation.

CONCLUSION: Cochlear implantation (CI) remains a safe procedure with a low complication rate. Nevertheless, advances in surgical techniques and the optimization of treatment modalities would further reduce complications. OBJECTIVE: To assess the complications of CI and describe the management of each complication encountered at our hospital. PATIENTS AND METHODS: This study involved 720 patients that underwent implantation from November 1988 through April 2007. Mean age at implantation was 13.6 years (range 12 months to 83 years). Patients were followed up regularly with a mean follow-up of 42 months (range 4-81 months). RESULTS: No death was attributed to device implantation. Major complications included: device failure in 12 patients, misplaced electrodes in 4, hematoma in 3, flap necrosis in 3, magnet displacement in 2, facial nerve twitching in 2, electrode exposure in 2, external auditory canal keratoma in 1, immediate facial nerve paralysis in 1, and skin flap irritation due to the suture material in 1. The overall major complication rate was 4.2% (30/720), and there were 37 minor complications (5.1%), which were resolved by conservative treatment or minor intervention. Minor complications included temporary vertigo in 17 patients, facial twitching in 11, hematoma in 4, subcutaneous emphysema in 3, and temporary facial nerve paralysis in 2.

Behavioral consequences of children with sleep-disordered breathing after adenotonsillectomy.

BACKGROUND: Adenotonsillectomy (AT) has been an effective treatment for sleep-disordered breathing (SDB) in children, and several studies described the risk of postoperative weight gain and obesity in children treated with AT. The present study aimed to evaluate behavioral improvements in children with SDB one year after adenotonsillectomy and to investigate an influence of postoperative weight gain on behaviors. METHODS: The study included 170 children aged 5-11 years who underwent adenotonsillectomy for SDB and 150 controls. Body mass index percentile was obtained for age and gender, and parental sleep-related breathing disorder (SRBD) questionnaire was used to assess the severity of SDB. Psychological assessment was performed pre- and post-adenotonsillectomy using standardized questionnaires including strength and difficulties questionnaire, children's depression inventory and screen for child anxiety-related emotional disorder. RESULTS: The mean age of 170 patients was 7.7 ± 1.5 years with 73 (42.9%) girls and 97 (57.1%) boys. The mean follow-up period were 15.4 ± 2.7 months. The patients had shown significant improvements in SDB scores as well as in questionnaire-based behavioral problems after adenotonsillectomy. The odds of a child being overweight were significantly increased after adenotonsillectomy. Less improvements in hyperactivity and conduct problems were observed in the patients with older ages, higher SRBD scores, and overweight/obesity at 1-year follow-up after adenotonsillectomy. CONCLUSION: These data suggest that abnormal behavioral outcomes should be evaluated postoperatively, which potentially could be reduced with the early adenotonsillectomy and adequate postoperative weight control.

Bilateral Congenital Cholesteatoma.

OBJECTIVE: To report the first large case series of extremely rare bilateral congenital cholesteatoma (CC). STUDY DESIGN: A retrospective cohort study. SETTING: University hospital otology referral clinic. PATIENTS: Six hundred four children with surgically confirmed CC. MAIN OUTCOME MEASURES: The bilateral CCs were compared with the unilateral CCs. RESULTS: The incidence of bilateral CC was 3.6% (22/615) per case or 1.8% (11/604) per child. Bilateral CC did not differ from unilateral CC regarding its demographics, and invasiveness by the proportion of advanced CC as 31.8% (7/22) versus 28.2% (167/594). But the invasiveness or location randomly differed between the ears, that advanced CC per child was higher as 45.4% (5/11). Bilateral exploration was attempted with a concern for hearing loss, which featured a combination of laser myringotomy to treat early CC and endaural laser-assisted single-stage inside-out cholesteatoma surgery to treat advanced CC. Bilateral exploration was difficult in three children with initially negative otoendoscopy. Among the seven advanced CC, proportion of anterior type was 71.4% (5/7), who all exhibited more than 20 dB HL, but two posterior type retained normal hearing. Therefore, bilateral advanced CCs of anterior origin showed poorest hearing outcome as bilateral more than 20 dB HL, which were in two children. Six second-look operations and one third-look operation were required to treat six residual CCs (30%) in four children (40%), including bilateral residual CC in two (20%); such reoperations were significantly more frequent than in unilateral CC. CONCLUSION: The diagnosis of bilateral CC required high index of suspicion from TBCT, and early bilateral exploration.

Biochemical markers of bone turnover in benign paroxysmal positional vertigo.

OBJECTIVE: Several studies have suggested a possible relationship between recurrent benign paroxysmal positional vertigo (BPPV) and altered calcium homeostasis in the endolymph of the inner ear. The present study aimed to evaluate the association between Ca2+ and vitamin D status and BPPV occurrence as well as the status of bone biochemical markers in osteoporotic patients who were diagnosed with idiopathic BPPV. METHODS: The study included total 132 patients who were referred to our clinic between August 2008 and October 2013. Based on the bone mineral density (BMD) results, the subjects were divided into three groups: normal BMD (n = 34), osteopenia (n = 40) and osteoporosis (n = 58). The biochemical markers of bone turnover including serum Carboxy-terminal telopeptide of type I collagen (s-CTX), osteocalcin, alkaline phosphatase (ALP) and urinary free deoxypyridinoline (u-DPD), were analyzed, along with the serum Ca2+ and vitamin D levels. RESULTS: The mean serum calcium, phosphate and creatinine clearance levels were within the standard laboratory reference range. The incidence of vitamin D deficiency was 11.8% (4/34) in the normal BMD group, 15% (6/40) in the osteopenia group and 43.1% (25/58) in the osteoporosis group. There was a positive correlation between the 25(OH)D and BMD results in the patients with BPPV. Among the bone turnover markers, the osteocalcin and u-DPD levels were significantly elevated in the osteoporotic patients with BPPV. Multiple logistic regression analyses showed that osteoporosis and vitamin D deficiency were associated with BPPV. CONCLUSION: Our findings suggest that the prevalence of BPPV in osteoporotic patients is associated with vitamin D deficiency and high bone turnover rates at systemic level, which could disturb local Ca2+ homeostasis in the inner ear.

Cochleariform Process Abutment on TBCT in Early Congenital Cholesteatoma.

OBJECTIVES: To study the influence of the cochleariform process abutment (CPA) of early congenital cholesteatomas (CC) (ECCs) on surgical outcomes. STUDY DESIGN: Retrospective case review. SETTING: University hospital otology referral clinic. PATIENTS: Two hundred consecutive pediatric ECC patients. INTERVENTIONS: The patients were classified into three groups based on the temporal bone computed tomography (TBCT) findings of ECC: A) the absence of CPA, B) the presence of CPA, and C) the presence of CPA and extension posterior to the malleus handle. MAIN OUTCOME MEASURES: Residual CC according to each of the TBCT and surgical stages during 34.9 ±â€Š20.1 months of follow-up. RESULTS: Group A was significantly associated with effortless delivery without matrix tearing (77%) even with simple myringotomy. Only 17% of group B experienced this outcome, and troublesome matrix tearing occurred in significantly more patients (p < 0.0001). Residual CCs were present in 17.5% of group B if matrix tears occurred, which was comparable to group C (22.0%) and significantly greater than group A (4.4%, p = 0.03). Normal hearing was preserved in 97.5% of the ECC patients both when the ECCs did not recur and when they recurred without CPA. However, residual ECCs with positive CPAs in five children (2.5%) required ossicle removal, and subsequent hearing loss. CONCLUSIONS: CPA is directly related to intraoperative matrix tear or increased recidivism, that CPA should be the landmark to distinguish stage II ECC from stage I. Surgeons should evaluate CPA on preoperative TBCTs of ECC patients, and restrict myringotomy approach to CPA negative ECC.

Hearing loss in postmenopausal women with low bone mineral density.

OBJECTIVE: Several studies suggested the possible relationship between decreased bone mineral density (BMD) of the temporal bone and hearing loss, primarily of the sensorineural type. The aim of the present study is to determine the relationship between BMD and hearing loss and to evaluate the systemic Ca(2+) and vitamin D status with relation to hearing sensitivity in the postmenopausal women who were diagnosed with primary osteoporosis. METHODS: The study involved a total of 324 patients who were referred between 2008 and 2013. Based on BMD scores, the subjects were divided into three groups: normal BMD (n=102), osteopenia (n=106) and osteoporosis (n=116). Hearing sensitivity was evaluated with audiometric tests along with serum Ca(2+) and vitamin D level. RESULTS: The age distribution among 3 groups was similar. Mean serum Ca(2+), phosphate, 25(OH)D and creatinine clearance were within the standard laboratory reference ranges in all patients. There was no difference in the proportion of vitamin D deficiency among groups. The typical type of hearing loss was sensorineural hearing loss (SNHL) and the patients with reduced BMD showed higher prevalence of SNHL than the patients with normal BMD. Pure-tone thresholds average was significantly higher in all frequencies in women with osteopenia/osteoporosis than women with normal BMD. Multiple logistic regression analyses showed that age and lumbar BMD were associated with the presence of hearing loss (>25dB). CONCLUSION: Our findings suggest that the presence of decreased BMD in postmenopausal women might be associated with the higher prevalence of age-related SNHL.

Transcanal CO2 laser-enabled ablation and resection (CLEAR) for intratympanic membrane congenital cholesteatoma.

OBJECTIVES: Cholesteatoma in the tympanic membrane is frequently regarded as congenital but there has been no case series review or comparison study with typical pediatric congenital cholesteatoma (CC). METHODS: All pediatric CC cases from 2009 to 2014 were collected, and a total of 10 cases of intratymapnic membrane CC (ICC) out of 429 CC cases were reviewed. They were compared with 14 cases of iatrogenic intratympanic membrane keratin after pediatric CC surgery (IIKC). RESULTS: ICC constituted 2.3% (10/429) of CCs, and the median age of operation was 24 months, 12 months earlier than that for CC. ICC failed to show male preference which is found in both CC and IIKC. As CC is commonly abutting the medial side of malleus, almost 90% of ICCs were found abutting the umbo of malleus. However, IIKC was usually located at the epithelial trauma site during the CC surgery without malleus abutment. Except in case of spontaneous resolution, the other cases of ICC and IIKC were treated by minimally invasive transcanal CO2 laser-enabled ablation and resection (CLEAR) alleviating any ossicle vibration trauma, incision or graft harvest. All patients retained normal hearing without complication and recurrence. CONCLUSION: ICC might be a rare variant of early detectable pediatric CC estimated from its location close to the ossicle and the surgical findings, but without sex preference. Although ICC shares morphologic similarity with IIKC, their locations of development are different, thereby suggesting different pathogenesis rather than epithelial injury. However, CLEAR surgery can be a good treatment option for intratympanic membrane lesions.

Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials.

Calcium is the most abundant mineral in human body and essential for the formation and maintenance of bones and teeth as well as diverse cellular functions. Calcium carbonate (CaCO3) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO3 is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO3 in comparison with that of bulk- or reagent grade nano CaCO3 in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO3 particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO3 nanoparticles were different from bulk CaCO3 or Ca2+ ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca2+ levels. Meanwhile, CaCO3 nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca2+ ions did. Biokinetic study revealed that the biological fate of CaCO3 particles was different from Ca2+ ions; however, in vivo, its oral absorption was not significantly affected by particle size. These findings provide crucial information to understand and predict potential toxicity and oral absorption efficiency of food grade nanoparticles.

The fate of calcium carbonate nanoparticles administered by oral route: absorption and their interaction with biological matrices.

BACKGROUND: Orally administered particles rapidly interact with biological fluids containing proteins, enzymes, electrolytes, and other biomolecules to eventually form particles covered by a corona, and this corona potentially affects particle uptake, fate, absorption, distribution, and elimination in vivo. This study explored relationships between the biological interactions of calcium carbonate particles and their biokinetics. METHODS: We examined the effects of food grade calcium carbonates of different particle size (nano [N-Cal] and bulk [B-Cal]: specific surface areas of 15.8 and 0.83 m(2)/g, respectively) on biological interactions in in vitro simulated physiological fluids, ex vivo biofluids, and in vivo in gastrointestinal fluid. Moreover, absorption and tissue distribution of calcium carbonates were evaluated following a single dose oral administration to rats. RESULTS: N-Cal interacted more with biomatrices than bulk materials in vitro and ex vivo, as evidenced by high fluorescence quenching ratios, but it did not interact more actively with biomatrices in vivo. Analysis of coronas revealed that immunoglobulin, apolipoprotein, thrombin, and fibrinogen, were the major corona proteins, regardless of particle size. A biokinetic study revealed that orally delivered N-Cal was more rapidly absorbed into the blood stream than B-Cal, but no significant differences were observed between the two in terms of absorption efficiencies or tissue distributions. Both calcium carbonates were primarily present as particulate forms in gastrointestinal fluids but enter the circulatory system in dissolved Ca(2+), although both types showed partial phase transformation to dicalcium phosphate dihydrate. Relatively low dissolution (about 4%), no remarkable protein-particle interaction, and the major particulate fate of calcium carbonate in vivo gastrointestinal fluids can explain its low oral absorption (about 4%) regardless of particle size. CONCLUSION: We conclude that calcium carbonate nanoparticles can act more actively with biological matrices in vitro and ex vivo, but that in vivo, their biological interactions and biokinetics are not affected by particle size.