Towards scalable and degradable bioplastic films from Moringa oleifera gum/poly(vinyl alcohol) as packaging material.

The use of plant gum-based biodegradable bioplastic films as a packaging material is limited due to their poor physicochemical properties. However, combining plant gum with synthetic degradable polymer and some additives can improve these properties. Keeping in view, the present study aimed to synthesize a series of bioplastic films using Moringa oleifera gum, polyvinyl alcohol, glycerol, and citric acid via thermal treatment followed by a solution casting method. The films were characterized using analytical techniques such as FTIR, XRD, SEM, AFM, TGA, and DSC. The study examined properties such as water sensitivity, gas barrier attributes, tensile strength, the shelf life of food, and biodegradability. The films containing higher citric acid amounts showed appreciable %elongation without compromising tensile strength, good oxygen barrier properties, and biodegradation rates (>95%). Varying the amounts of glycerol and citric acid in the films broadened their physicochemical properties ranging from hydrophilicity to hydrophobicity and rigidity to flexibility. As all the films were synthesized using economical and environmentally safe materials, and showed better physicochemical and barrier properties, this study suggests that these bioplastic films can prove to be a potential alternative for various packaging applications.

Polyimide-Based Membrane Materials for CO2 Separation: A Comparison of Segmented and Aromatic (Co)polyimides.

A series of new poly(ethylene oxide) (PEO)-based copolyimides varying in hard segment structure are reported in this work as CO2 selective separation membranes. Their structural diversity was achieved by using different aromatic dianhydrides (4,4'-oxydiphthalic anhydride (ODPA), 4,4'-(hexafluoroisopropylidene)diphthalic anhydride (6FDA)) and diamines (4,4'-oxydianiline (ODA), 4,4'-(4,4'-isopropylidene-diphenyl-1,1'- diyldioxy)dianiline (IPrDA), 2,3,5,6-tetramethyl-1,4-phenylenediamine (4MPD)), while keeping the content of PEO (2000 g/mol) constant (around 50%). To get a better insight into the effects of hard segment structure on gas transport properties, a series of aromatic polyimides with the same chemistry was also studied. Both series of polymers were characterized by 1HNMR, FTIR, WAXD, DSC, TGA, and AFM. Permeabilities for pure He, O2, N2, and CO2 were determined at 6 bar and at 30 °C, and for CO2 for pressures ranging from 1 to 10 bar. The results show that OPDA-ODA-PEO is the most permeable copolyimide, with CO2 permeability of 52 Barrer and CO2/N2 selectivity of 63, in contrast to its fully aromatic analogue, which was the least permeable among polyimides. 6FDA-4MPD-PEO ranks second, with a two times lower CO2 permeability and slightly lower selectivity, although 6FDA-4MPD was over 900 times more permeable than OPDA-ODA. As an explanation, partial filling of hard domain free voids by PEO segments and imperfect phase separation were proposed.

Continent catheterizable conduits in pediatric urology: One-center experience.

BACKGROUND: Clean intermittent catheterization (CIC) is a standard treatment for patients who are unable to empty the bladder. In the absence of the urethra or if catheterization through the urethra is problematic, a continent vesicostomy is used as a catheterizable conduit. The Malone procedure is an established treatment option for children with neurogenic constipation and fecal incontinence. OBJECTIVES: The aim of the study was to report the authors' experience with continent catheterizable conduits (CCCs) in children, to review the results and to determine the efficacy of the technique, with an emphasis on continence and the need for revision. MATERIAL AND METHODS: The retrospective study involved children who underwent catheterizable conduit procedures from 2000 to 2015. Two kinds of continent stomas were performed: Mitrofanoff vesicostomies for CIC and Malone antegrade continence enemas (MACEs). The 115 patients treated included 66 girls and 49 boys. A total of 134 operations were performed; 62 were Mitrofanoff vesicostomies and 72 were Malone appendicostomies. In 19 cases, both Mitrofanoff and Malone appendicostomies were formed out of 1 appendix divided into 2 parts. In 5 children vesicocutaneous stomas were constructed using Monti's procedure, and in 1 it was constructed from an intussuscepted ileal loop. In 27 patients Malone procedures were performed laparoscopically. RESULTS: The mean follow-up period was 8.6 years. There was no serious morbidity in relation to the surgery. In 9 children local wound infection was noted, and in 9 others stomal stenosis developed. Out of the 62 children with catheterizable vesicostomies, 59 were continent. The MACE procedure was successful in all 72 patients; problems with constipation and fecal incontinence were resolved in all cases. None of the laparoscopies needed conversion. CONCLUSIONS: Continent catheterizable conduits help patients achieve both fecal and urinary continence. Laparoscopy is effective in performing the Malone procedure. Stoma-related complications could be avoided using end-to-side appendix anastomoses to the skin. Stomal incontinence is rare even when a simplified technique is employed, using the appendix without cecoplication.

Interactive computations: toward risk management in interactive intelligent systems.

Understanding the nature of interactions is regarded as one of the biggest challenges in projects related to complex adaptive systems. We discuss foundations for interactive computations in interactive intelligent systems (IIS), developed in the Wistech program and used for modeling complex systems. We emphasize the key role of risk management in problem solving by IIS. The considerations are based on experience gained in real-life projects concerning, e.g., medical diagnosis and therapy support, control of an unmanned helicopter, fraud detection algorithmic trading or fire commander decision support.

FORMULATION AND EVALUATION OF MICROSPHERES CONTAINING LOSARTAN POTASSIUM BY SPRAY-DRYING TECHNIQUE.

Despite numerous applications of microspheres, few works devoted to the preparation of microspheres containing cardiac medications have been published. This study presents the potential of receiving microspheres containing losartan potassium, based on a matrix containing Eudragit L30D55. The study focuses on the possibilities of controlled release of losartan potassium from microspheres in order to reduce the dosage frequency, and also provides information on the effect of the addition of excipients to the quality of the microspheres. Microspheres are monolithic, porous or smooth microparticles ranging from 1 to 500 microns in size. For the preparation of microspheres containing losartan potassium, the spray-drying method was used. The performed study confirmed that the spray-drying technology used to obtain microspheres meets the criteria of size and morphology of the microparticles. The assessment of the kinetics of losartan potassium release from the examined microspheres demonstrated that the release profile followed the first- and/or zero-order kinetics. The use of spray-drying techniques as well as Eudragit L30D55 polymer matrix to obtain the microspheres containing losartan potassium makes it possible to obtain a product with the required particle morphology and particle size ensuring the release of the active substance up to 12 h.

Influence of spray drying manufacturing parameters on quality of losartan potassium microspheres.

A general aim of the research was to develop a technology of manufacturing microspheres with losartan potassium as an active substance, and Eudragit L30D55 as a matrix with the use of spray drying technique. During the first step of the study, optimal values of parameters in spray drying process were established (i.e., operating temperature, peristaltic pump performance, aspiration value). Those values have a crucial effect on morphological parameters, and the size and homogeneity of received particles. In the obtained microspheres, the activity of excipients, which modify morphological properties of microspheres, were tested. Additionally, we studied the impact of the type and amount of plasticizer, as well as the amount of an adopted polymer in proportion to dry matter of losartan potassium, on quality of final product. Triethyl citrate and citric acid, plasticizers tested in reported studies, were also verified. A detailed study of the influence of both plasticizers on the qualities of microspheres containing losartan potassium on Eudragit L30D55 matrix indicated a positive influence of triethyl citrate and a negative influence of citric acid on morphological properties, shape and size of particles. The application of optimal parameters of spray drying and triethyl citrate as a plasticizer in the amount of 10 to 15% allows to obtain microspheres from 1.27 to 7.24 µm.

Morphological and enzymatic changes caused by a long-term treatment of female rats with a low dose of gonadoliberin agonist and antagonist.

BACKGROUND: Long-term treatment with gonadoliberin analogs is used to block the hypothalamic-pituitary-gonadal axis. The use of these agents is generally considered to be safe; however, some observations suggest the possibility of adverse effects. MATERIAL/METHODS: We investigated whether a 3-months administration of a low dose (6 µg/kg b.w.) of dalarelin - a new agonist, and cetrorelix - a known antagonist of GnRH to female rats causes morphological changes in pituitary gland, ovaries, uterus and liver (HE and VG staining); effects on pituitary, hepatic and blood enzyme activities (histochemical and kinetic methods, respectively), and on the blood lipid profile (colorimetric methods); and to what extent these changes are reversible. RESULTS: Applying analogs effectively inhibited ovulation, affected the uterine endometrium and changed histological appearance of the liver (e.g., steatosis). They altered activities of marker enzymes of cellular respiration, gluconeogenesis and intracellular digestion in the liver and, partially in the pituitary gland, caused undesirable changes in the activities of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and creatine kinase, and a concentration of cholesterol HDL fraction and triglycerides in the blood. Both morphological and enzymatic effects were more evident after antagonist administration; changes in the blood lipid profile were more evident after agonist administration. In both analogs histological and enzymatic changes persisted a relatively long time after the discontinuation of the treatment. CONCLUSIONS: The low dose of dalarelin and cetrorelix is sufficient to cause limited damage of hepatic cells and may modify the function of pituitary, ovaries, uterus and liver as well as other organs, even after discontinuation of the treatment.

[Epidemiological and demographic analysis of indications for Baha® surgery in Poland--multicenter study]. / Analiza epidemiologiczna i demograficzna wskazan do implantacji systemu Baha® w Polsce--badanie wieloosrodkowe.

AIM OF THE STUDY: To collect and analyze epidemiological and demographical data of patients qualified for and implanted with the Baha® system in Poland. MATERIAL AND METHOD: 17 out of 28 otolaryngology departments performing Baha® implantation in Poland participated in the study. Up to date there were 286 patients registered in database. Data were obtained from the preoperative questionnaires including information such as age and gender, indications for the implantation, previous hearing aid use as well as data regarding the surgical technique. RESULTS: The most frequent indication for the Baha® system was bilateral mixed hearing loss (51%), followed by SSD (18%), bilateral conductive hearing loss (17%), unilateral mixed (8%) and conductive (6%) hearing loss. In 11% of subjects hearing impairment was congenital versus 89% cases of acquired. The mean age was 44 years with the slight prevalence of women (52%). 63% of patients did not have previous experience with hearing aids. The most frequent surgical technique was classic dermatome single stage procedure performed under general anesthesia (65%). CONCLUSIONS: Data gather in this multicentre research serve as a valuable source of information on qualifications for the Baha®, shows demographic spectrum of adult recipients in Poland. It also presents the preferences of surgical procedures. Outcomes of the study may constitute a reference for each centre participating in this research as well as for new centers starting the Baha® procedure.

Expression of arachidonate metabolism enzymes and receptors in nasal polyps of aspirin-hypersensitive asthmatics.

BACKGROUND: The pathogenesis of rhinosinusitis in aspirin-exacerbated airway disease is closely linked to the disequilibrium in arachidonic acid metabolism. Although considerable amounts of data concerning impaired eicosanoid production are available, the precise mechanism and pathogenesis of the disease are still unknown. The aim of the present study was to assess the expression of enzymes belonging to the arachidonic acid cascade and receptors for arachidonate derivative metabolites in nasal polyps from aspirin- hypersensitive (AH) and aspirin-tolerant (AT) patients with rhinosinusitis. METHODS: Cells expressing cysteinyl leukotriene (CysLT) receptors (CysLT(1) and CysLT(2)), arachidonate 5-lipoxygenase, leukotriene B(4) receptor type 1, E-prostanoid receptors (EP(2) and EP(4)), cyclooxygenase (COX)-1 and COX-2 were detected by immunocytochemistry in nasal polyps obtained from 10 AH patients and 18 AT patients. RESULTS: There was a significantly higher density of cells expressing CysLT(1) and CysLT(2) receptors in nasal polyps from AH patients than from AT patients (p < 0.001). In contrast, the density of cells expressing EP(2) receptor and COX-2 was significantly lower in AH patients than in AT patients (p < 0.02). The number of COX-2-positive epithelial cells was significantly reduced in AH polyps (p < 0.04). CONCLUSIONS: The elevated number of nasal polyp cells expressing CysLT receptors and lack of cells expressing EP(2) receptor and COX-2 may be related to a more severe course of hyperplastic rhinosinusitis in aspirin hypersensitivity.

Participation of mast cells in chronic otitis media.

In the pathogenesis of chronic otitis media (COM), much attention is paid to the molecular mechanisms of local inflammatory reactions in which mast cells (MCs) may be involved due to their role not only in allergic but also inflammatory processes. The aim of this study was to assess the density of mast cells in chronic otitis media in relationship to different clinical courses of COM, bacterial infections and types of disease. The MCs expression was measured immunohistochemically in paraffin-embedded granulation tissue specimens taken during surgery, by staining with a monoclonal antibody against tryptase. The density of tryptase-positive mast cells was lower in tissue samples from the group with a good clinical course than in those from the group with poor healing and recurrence (p = 0.006). There were no differences between the groups of patients with granulomatous and cholesteatomatous chronic otitis media (p = 0.66) or between the groups of patients with and without bacterial infection (p = 0.30), although the density of mast cells was lower for those with Pseudomonas aeruginosa/Proteus sp./ /Staphylococcus MRSA infection. In conclusion, the expression of mast cells in chronic otitis media granulation tissue was found to differ depending on the clinical course of the disease, but not on bacterial infection or type of COM. This may suggest that mast cells contribute to the maintenance of the inflammatory process, but not to antibacterial defense in chronic otitis media.

Transverse testicular ectopia with abnormal karyotype - a case report.

OBJECTIVES: Growth disturbances and developmental malformations of external genitalia, such as hypospadias, bifid scrotum and micropenis, coexisting with non-palpable testes, may develop as a result of primary endocrinological dysfunctions as well as an effect secondary to chromosomal aberrations. Therefore, patients with these symptoms require specific diagnostic and therapeutic approaches. DESIGN AND METHODS: We present an example of TTE as a presentation of karyotype abnormalities. Clinical presentation - 9.5 year old boy presented with hypospadias, bilateral cryptorchidism and right inguinal hernia and short stature. RESULTS: Endocrine test showed low testosterone levels with adequate gonadal response. Laparoscopy was performed and revealed the presence of TTE. CONCLUSIONS: The presence of mosaic karyotype with abnormal Y chromosome does not exclude a possibility of testis migration disorders, including TTE, caused by other (possibly genetic) factors. Laparoscopy is a technique of choice for diagnosis and treatment in cases of cryptorchidism.

Impact of micelle ionic electrical double layer structure on the excited state protolytic reaction in the fluorescent probe bound to the colloidal nanoparticles.

The fluorescent probe, 2-hydroxynaphthalene(dodecylo)-6-sulfonamide (NSDA) bound selectively to shear plane of various electrostatic charges was synthesized and its photophysical properties have been investigated by means of steady state fluorescence and nanosecond time-resolved spectroscopy. Our experimental data allowed us to determine the excited state proton transfer (ESPT) rate and equilibrium constants of NSDA bound to micelles and to estimate the electric potential value (Ψ) at the particle surface. The spatial dependence of proton movement velocity through electric double layer (EDL) of micelles has been thoroughly analyzed. In this article, a new approach of estimating the values of the micelle potential (Ψ(R)) from the excited state proton transfer rate constant of the fluorescent probe bound at a certain distance (R) to a micellar surface has been proposed. The Ψ(R) values, obtained in this way, are compared with electrophoretic values of the particle potential (ζ). Our results on electrophoretic potentials and the reaction course of the ESPT in colloidal environment may contribute to a deeper understanding of micellar interactions and behavior of the living cells in contact with various diluted substances such as pharmacological drugs, hormones, proteins, and other colloidal particles.

[Nonimmune hydrops fetalis associated with congenital small bowel atresia--a case study]. / Nieimmunologiczny obrzqk plodu w przebiegu wrodzonej niedroznosci jelit--analiza przypadku klinicznego.

Nonimmune hydrops fetalis is observed with the frequency of 1:3000 cases diagnosed pre- and postnatally. In the following paper the authors analyzed the course of pregnancy complicated by fetal ascites and polyhydramnios with the appearance of colonic ileus and they presented the postnatal condition of the baby The preliminary diagnosis was confirmed after birth and the newborn was operated in the second day of his life. The congenital small bowel atresia was qualified as a III B type (Grossfeld qualification), which is called the "pagoda" syndrome [3]. The colonic atresia is located then around the superior mesenteric vessels, which leads to colonic necrosis (Figure 1).

[Subjective intraoperative hearing self-assessment in patients after stapedotomy comparing to postoperative pure-tone audiometry]. / Subiektywna sródoperacyjna poprawa sluchu u chorych po stapedotomiach w porównaniu z wynikiem kontrolnego badania sluchu w audiometrii tonalnej progowej.

UNLABELLED: In otosclerosis patients the most common procedure followed at Otosurgical Dept. Medical University of Lodz is stapedotomy with insertion of teflon-piston prosthesis. When surgery is finished a whisper hearing test is done from the 1 meter distance for brief intraoperative hearing improvement assessment. There is a number of patient who report subjective intraoperative hearing improvement which is not confirmed by postoperative pure-tone audiometry (2-3rd post-op day). THE AIM OF THE STUDY: was the analysis of factors influencing stapedotomy (teflon-piston procedure) patients in which intraoperative hearing improvement was not confirmed by postoperative pure-tone audiometry. MATERIAL AND METHOD: Retrospective analysis of postoperative hearing results in patients who underwent stapedotomy (teflon-piston operation) at the Otosurgical Dept. Medical University of Lodz from 2005 to 2009. RESULTS: The total number of 142 stapedotomies were analyzed. In 27 ears no hearing improvement was reported (19.1%). Among them 18 reported intraoperative hearing improvement not confirmed on postoperative pure-tone audiometry and 9 cases intraopertively reported no hearing improvement. Patients in Group A (hearing improvement 1-2 month post stapedotomy)--12 cases (44.4%) with hearing improvement confirmed by pure-tone audiometry and Group B--5 cases (55.6%) in which no sign of hearing improvement in pure-tone audiometry was reported. CONCLUSION: In patients who intraopertively reported hearing improvement not supported by the pure-tone audiometry the following factors seem to play a vital role: a) strong suggestion and willingness of improvement after surgical treatment, b) specific condition of the whisper hearing test at the operating room environment, c) patient's stress during the surgery and strong fear of possible revision surgery.

Congenital midgut volvulus associated with fetal anemia.

Congenital volvulus is a life-threatening condition, both for the fetus and for the newborn. A volvulus is a twist of small bowel loops or a proximal part of the colon around the mesenteric artery or its branches. The potential consequences of volvulus are ileus and necrosis of the intestinal wall. Prenatal diagnosis of midgut volvulus is difficult. It should be suspected antenatally when polyhydramnios, intestinal dilatation, ascites and/or signs of fetal anemia are present on ultrasound assessment. We report a case of a congenital midgut volvulus associated with fetal anemia. The fetal ultrasound performed at 32 weeks' gestation showed a polyhydramnios, hydrothorax, thick ascites accumulation around the liver and the suspicion of a dilated bowel loop. Additionally, Doppler examination showed an increased value of peak systolic velocity in the middle cerebral artery. Cordocentesis confirmed significant fetal anemia. At 34 weeks, because of the suspicion of idiopathic meconium ileus and secondary anemia, a Cesarean section was performed after the administration of steroids. During the laparatomy, performed postnatally, a midgut volvulus was diagnosed. The affected portion of the ileum was resected and end-to-end anastomosis performed. An antenatal diagnosis of midgut volvulus should be considered when signs of fetal anemia, including an increased value of peak systolic velocity in the middle cerebral artery, are present with polyhydramnios, fetal ascites, dilated bowel loops on antenatal ultrasound. An assessment of the fetal hemodynamic status should be a part of the ultrasound assessment for patients with nonspecific fetal bowel pathologies, including congenital volvulus.

Influence of surfactants of Rofam type on properties of piroxicam tablets.

Possibilities of application of non-ionic surfactants of Rofam type as solubilizers for piroxicam poorly dissolved in water were assessed. Homologous series of Rofams containing oxyethylene segments from 3 to 18 were used in the study. Tablet formulation was made by wet granulation technique using these surfactants in order to improve drug dissolution properties. Influence of both quantity and type of Rofam on morphological parameters of granules and tablets was investigated. All the examined parameters met the pharmacopeal norms. Paddle method was used to evaluate piroxicam pharmaceutical availability. The presence of non-ionic surfactants in composition of tablet mass improved dissolution rate of piroxicam.

[Evaluation of apoptosis expression in granulation tissue in chronic otitis media]. / Ocena ekspresji markerów apoptozy w ziarninie w przewleklym zapaleniu ucha srodkowego.

INTRODUCTION: There is a growing evidence that molecular and cellular mechanisms may play a role in pathogenesis in chronic otitis media. THE AIM OF THE STUDY: was to determine the intensity of apoptosis in granulation tissue in chronic otitis media. MATERIAL AND METHOD: Fifty four patients with chronic otitis media, who underwent surgical treatment, were enrolled into the study. The apoptosis was measured in paraffin-embedded granulation tissue specimens by an immunohistochemical methods, by staining with a monoclonal antibody against apo-1/Fas/CD95 and P53 protein. The bacteriological evaluation of middle ear discharges were also done. RESULTS: It was found statistically significant difference in expression of apo-1/Fas antigen between the groups with good clinical course (good healing and without recurrence) than those in the group with poor healing and recurrence (mean percentage of immunopositive cells 1.52 vs 3.34 respectively, p<0.001). The activity of apo-1/Fas antigen was more intense in tissue samples from the group with bacterial infection caused by Pseudomonas aeruginosa/Proteus sp/Staphyloccocus MRSA than those in the group without this infection (mean percentage of immunopositive cells 3.78 vs 1.75 respectively, p<0.001). The differences were also observed for P53 protein expression between the same groups, however they were not significant. There was no differences between the groups of patients with granulomatous and cholesteatomatous chronic otitis media. The significant negative correlation was found between expression of apo-1/Fas antigen and expression of P53 protein (r=-0.64, p<0.001). CONCLUSIONS: In granulation tissue in chronic otitis media different expression of apo-1/Fas antigen was found in relationship to clinical course of disease and bacterial infection caused by Pseudomonas aeruginosa/Proteus sp/Staphyloccocus MRSA. It may suggest that apoptosis mediated by apo-1/Fas mechanism may contribute to pathogenesis of chronic otitis media.

[Own experience in stapes revision surgery--analysis of indications]. / Retrospektywna analiza przypadków reoperacji w stapedotomiach i stapedektomiach--doswiadczenia wllasne.

AIM: Analysis of indications for stapes revision surgery in patients qualified for the secondary procedure at the Otosurgery Dept. Medical University of Lodz. MATERIAL AND METHODS: 25 cases of stapes revision surgery out of the 385 total treated surgically otosclerosis cases are discussed. RESULTS: In group A (patients after total stapedectomy) the following indications for the secondary surgical procedure were observed: 12 cases--platinum wire prosthesis displacement with ossicular chain discontinuity; 3 cases--perichondrium or adipose tissue atrophy; 2 cases of incudo-stapedial joint luxation. Group B was composed of 8 patients after stapedotomy (teflon piston operation, 0.6 mm). CONCLUSIONS: (1) The most common indication for the stapes revision surgery in patients after total stapedectomy were prosthesis displacement and necrosis of the long crus of the incus. (2) Obliteration of the stapes footplate after small fenestra operation was observed in our material to be the most frequent indication for the secondary stapes procedure.

[Does the material of stapes prosthesis influence hearing improvement in stapes surgery--retrospective analysis of 350 cases]. / Wplyw rodzaju protezki strzemiqczka na stopien poprawy sluchu w chirurgii strzemiaczka--analiza retrospektywna 350 przypadków.

AIM: Retrospective analysis of the post-op hearing results in stapes surgery using different types of materials for stapes prosthesis after 12 months follow up. MATERIAL AND METHODS: The total number of 350 otosclerosis patients who underwent surgical treatment at the Otosurgery Department, Medical University of Lodz from 1980-2002. All patients included in the study were divided into 4 groups: group 1 (N=54)--Portmann's method interposition, group 2 (N=160)--stapes replaced with the Shea-type prosthesis, group 3 (N=60)--platinum wire prosthesis (Zini-type), group 4 (N=76)--teflon-piston operation (Fisch-type). RESULTS: The 12 months post-op mean value for air-bone gap (500, 1000, 2000 Hz) presented the following values: group 1-19 dB, group 2-15.9 dB, group 3-18.4 dB, group 4-13.5 dB. The percentage of patients with the mean air-bone gap value of 15 dB or less (500, 1000, 2000 Hz) has the following values in each group: group 1-75%, group 2-81.3%, group 3-83%, group 4-85%. CONCLUSIONS: 12 months post-op hearing results compared between the 4 studied groups showed statistically not significant differences. Our experience with teflon-piston prosthesis shows the lowest post-op mean value of the air-bone gap.