Neutrophils are consistently associated with arterial thrombotic morbidity in human clinical studies but the causal basis for this association is unclear. We tested the hypothesis that neutrophils modulate platelet activation and thrombus formation in vivo in a cathepsin G-dependent manner. Neutrophils enhanced aggregation of human platelets in vitro in dose-dependent fashion and this effect was diminished by pharmacologic inhibition of cathepsin G activity and knockdown of cathepsin G expression. Tail bleeding time in the mouse was prolonged by a cathepsin G inhibitor and in cathepsin G knockout mice, and formation of neutrophil-platelet conjugates in blood that was shed from transected tails was reduced in the absence of cathepsin G. Bleeding time was highly correlated with blood neutrophil count in wildtype but not cathepsin G deficient mice. In the presence of elevated blood neutrophil counts, the anti-thrombotic effect of cathepsin G inhibition was greater than that of aspirin and additive to it when administered in combination. Both pharmacologic inhibition of cathepsin G and its congenital absence prolonged the time for platelet thrombus to form in ferric chloride-injured mouse mesenteric arterioles. In a vaso-occlusive model of ischemic stroke, inhibition of cathepsin G and its congenital absence improved cerebral blood flow, reduced histologic brain injury, and improved neurobehavioral outcome. These experiments demonstrate that neutrophil cathepsin G is a physiologic modulator of platelet thrombus formation in vivo and has potential as a target for novel anti-thrombotic therapies. Human clinical studies consistently link greater blood leukocyte count to increased risk of atherothrombotic disease events, such as myocardial infarction (MI) and stroke 12/13Cathepsin G is one of multiple plausible molecular mediators of the association between leukocytes and thrombotic vascular occlusion We hypothesized that neutrophil cathepsin G is a physiologic platelet activator and key molecular mediator of vascular thrombus formation in vivo. We tested these hypotheses in experiments using both human and mouse blood and three separate mouse models of vascular thrombus formation in vivo. The aim of these studies was to identify a molecular mechanism that directly links neutrophils to arterial thrombosis and to determine the relevance of cathepsin G as a potential target for anti-thrombotic therapies.Healthy male and female volunteers  were enrolled to examine human platelet aggregation in vitro. Volunteers were eligible for study participation if they were free of chronic and acute medical illness and had not taken aspirin or nonsteroidal anti-inflammatory drugs in the past 10 days. This study was approved by the Johns Hopkins Institutional Review Board and all participants signed written informed consent.3 neutrophils/µl) with the freshly-prepared PRP (1.7×105 platelets/µl) and maximum platelet aggregation was determined after stimulating samples for 5 min at 37°C with thrombin receptor activating peptide-6  in a dual channel lumi-aggregometer . In some experiments, PAR4 agonist peptide  was also added to stimulate platelet aggregation. The effect of neutrophil count on platelet aggregation was assessed by varying the number of neutrophils present in PRP through the pathophysiologic range (0–20×103 neutrophils/µl).Platelet aggregation was assessed in platelet rich plasma (PRP) by impedance aggregometry in the presence and absence of neutrophils and a specific cathepsin G inhibitor, cathepsin G inhibitor I 3/µl) were reconstituted with freshly prepared PRP (1.7×105 platelets/µl) and maximum aggregation in response to TRAP determined by impedance aggregometry as described above.HL60 cells , an immortalized myelocytic cell line, were cultured in RPMI 1640/20% fetal calf serum  and 1.5% DMSO to induce neutrophil differentiation 5 platelets/µl), before and after stimulating platelet aggregation with 15 µM TRAP. Knock-down of cathepsin G expression in HL60 cells was also confirmed by Western blotting. Briefly, PRP supernatant or HL-60 cells were treated with lysis buffer containing 150 mM NaCl, 50 mM Tris-HCl, 2 mM EDTA, 0.1% sodium dodecyl sulfate (SDS) and inhibitor cocktail . Proteins were boiled for 5 minutes and proteins separated (10 µg/lane) by 10% SDS-polyacrylamide gel electrophoresis. Nitrocellulose membranes  were blocked with 10% nonfat dry milk/0.1% Tween-20 and incubated overnight at 4°C with mouse anti-human cathepsin G  or rabbit polyclonal β-actin IgG antibody , followed by HRP-conjugated goat anti-mouse IgG antibody  or goat anti-rabbit IgG-HRP antibody . Proteins were visualized by enhanced chemiluminescence .Western blotting was used to quantify cathepsin G protein in human PRP, in the presence and absence of neutrophils  were used to examine platelet-mediated thrombus formation in vivo using three distinct models: tail bleeding time, mesenteric arteriolar thrombus formation, and collagen-coated filament occlusion of the middle cerebral artery (MCA). Cathepsin G deficient (CatG−/−) mice that were backcrossed for 10 generations on a C57BL/6 background were the generous gift of Dr. Timothy Ley . Strain characterization of backcrossed mice  identified >98% of chromosomal markers belonging to this strain. Mouse studies were approved by the Johns Hopkins University Animal Care and Use Committee .The distal 5 mm of tail was amputated from anesthetized mice (ketamine 100 mg/kg IM injection) and the tail immersed in 37°C phosphate-buffered-saline. Time to visible cessation of bleeding was recorded in wildtype (WT) mice injected intravenously with vehicle , cathepsin G inhibitor I , or aspirin , and in CatG−/− mice.Blood neutrophil counts in vivo were increased by treating mice with mouse recombinant granulocyte colony stimulating factor  (1 µg subcutaneous injection×3 consecutive days) and decreased by treatment with cyclophosphamide (Sigma) . Complete blood counts were determined by automated cell counter  and leukocyte differential verified by manual cell counting. Cell counts and bleeding times, as described above, were determined on the day of the third GCSF  injection. Blood monocyte counts were manipulated in vivo by intaperitoneal injection of a monocyte depleting IgG antibody against CCR2, MC21 , or isotype control antibody, IgG2b  Neutrophil-platelet conjugate formation was assessed by flow cytometry in WT and CatG−/− mouse blood in vivo and in vitro as previously described with modification 8 platelets) into an anesthetized (ketamine [100 mg/kg]/xylazine [10 mg/kg] IM injection) recipient mouse. In another set of experiments, native platelets were labeled in vivo by intravenous injection of X488 , a fluorescently labeled IgG derivative against mouse GPIbβ that does not alter platelet adhesion or aggregation 3 (15%)-soaked piece of Number 2 Whatman paper onto the arteriolar surface for 90 sec. Fluorescent images of platelet accumulation onto the injured vascular surface were captured with a digital camera  and analyzed with imaging software . Time to vascular occlusion  by platelet thrombus was determined for WT and CatG−/− mice in the presence and absence of cathepsin G inhibitor I  or aspirin .Ferric chloride-induced mesenteric arteriolar thrombosis was assessed by intravital fluorescence microscopy as previously described with modification Transient filament occlusion of the MCA was performed as previously described with modification Data are mean ± SD unless otherwise indicated. Data were analyzed by t-test or analysis of variance (ANOVA) with Bonferroni correction for multiple post-hoc comparisons, as appropriate. Correlations between leukocyte counts and bleeding times were determined by parametric (ln[count]) and nonparametric (raw count) methods with similar results. All significance testing was two-tailed and results considered significant at an alpha of 0.05.Reconstitution of human neutrophils with autologous PRP increased agonist-induced platelet aggregation by ∼50% fig. 1A.We hypothesized that cathepsin G inhibitor I antagonized the pro-aggregatory effect of neutrophils by blocking the effect of neutrophil cathepsin G on platelet PAR4. To test this hypothesis we repeated aggregation experiments in the presence of a maximal dose of PAR4 agonist peptide, which exerts its platelet activating effect downstream of the enzymatic activity of cathepsin G. PAR4 peptide did not significantly increase platelet aggregation over TRAP alone in the absence of neutrophils , suggest3/µl. We performed Western blotting experiments on plasma from aggregation samples to confirm release of cathepsin G from neutrophils. These experiments demonstrated that the increase in platelet aggregability related to neutrophils was associated with an increase in the plasma concentration of cathepsin G in the presence of TRAP-activated, but not unactivated, platelets  or bind fibrinogen  in response to collagen stimulation in vitro among the four treatment conditions , consistent with the effects of GCSF and cyclophosphamide being specific to neutrophil count and not to an alteration in platelet function. Furthermore, because monocytes share multiple molecular pathways with neutrophils and have been reported to contribute to thrombus formation We compared the effect of cathepsin G inhibitor I on bleeding time to the effect of aspirin. Dose-response studies demonstrated that aspirin was maximally effective at prolonging tail bleeding time at an intravenous dose set to approximate a blood concentration of 500 µM fig. 4A,We next examined the effect of cathepsin G on platelet thrombus formation under arterial flow conditions in mesenteric microvessels. As previously described Comparing CatG−/− to WT mice provided results similar to those obtained with pharmacologic inhibition of cathepsin G- i.e., time to thrombus formation was prolonged in knockout mice (The impact of cathepsin G on CBF and ischemic brain injury was examined using a previously described mouse stroke model These experiments demonstrate the physiologic importance of neutrophils to platelet activation and vascular thrombus formation in vivo and its mechanistic dependence on cathepsin G. The ability of neutrophil cathepsin G to promote platelet aggregation and vascular occlusion was demonstrated in human PRP in vitro, after tissue trauma in the mouse in vivo, under arterial flow conditions in mouse microvessels, and in a vascular occlusive stroke model. Specificity of effect was demonstrated using both a pharmacologic inhibitor of cathepsin G, which provided effective inhibition at submicromolar concentrations and in a dose-dependent manner, and in cathepsin G deficient mice. These translational research experiments provide a direct causal mechanism to help explain the strong association between neutrophil count and arterial thrombotic morbidity previously described for patients with atherosclerosis There was a striking dose-response relation between neutrophil count and both platelet activation in vitro and bleeding time in vivo. In human PRP, this dose-response relation was observed at neutrophil counts within the range clinically encountered under physiologic and pathologic conditions. The pro-aggregatory effect of neutrophils was markedly reduced in the absence of cathepsin G activity, whether induced pharmacologically or by expression knockdown. The effect of neutrophil cathepsin G on platelet aggregation appeared to be mediated in part by cleavage of PAR4 because inhibition of cathepsin G activity failed to diminish the pro-aggregatory effect of neutrophils when PAR4 agonist peptide was used to activate platelets. Our data suggest that cathepsin G acts as a physiologic platelet activator in the blood milieu whose availability is regulated, in part, by the number of accessible neutrophils. However, the impact of neutrophils on platelet aggregation may involve mechanisms in addition to the action of cathepsin G on PAR4 because abrogation of the pro-aggregatory effects of neutrophils appeared incomplete at high neutrophil counts and in knockdown experiments with HL60 cells. Additional mechanisms through which neutrophils may promote platelet aggregation include release of prostaglandin metabolites The ability of neutrophils to form mixed aggregates with platelets is well recognized In vivo, the number of blood neutrophils appeared to modulate the speed with which hemostasis could be achieved after traumatic injury in the mouse. Bleeding time was highly and inversely correlated with the neutrophil count but showed no association with lymphocyte, monocyte, or platelet counts. These data should not be construed to mean that these other cell types have no influence on hemostasis; platelets are well recognized to play a key role in primary hemostasis, and monocytes have been reported to influence clot formation through formation of tissue factor bearing microparticles Neutrophils have long been recognized to possess multiple mechanisms with potential to both promote The discovery of a cathepsin-G-dependent relationship between neutrophil count and thrombus formation in vivo has important clinical implications. Given that acute stress is accompanied by demargination of neutrophils and a rapid rise in blood neutrophil count, it might be reasonable to postulate that neutrophilia offers a protective mechanism to promote hemostasis under conditions of traumatic injury. While potentially protective, a pro-thrombotic effect from neutrophil cathepsin G might increase risk of pathologic thromboses in individuals with pre-existing pro-thrombotic states as has been described for patients with atherosclerosis In sum, our data indicate that neutrophil cathepsin G is a physiologic regulator of platelet activation and thrombus formation in vivo. Our experiments suggest that cathepsin G is a potential target for novel anti-thrombotic therapies, but like all such therapies, inhibition of cathepsin may increase bleeding risk as well. Additional experiments are needed to determine the potential benefits and risks of cathepsin G inhibitors in animal models of vascular occlusive diseases.


The spinous process (SP) of the seventh cervical vertebra (C7) is characterized as the most prominent, which makes it an anatomical landmark for the recognition of other SPs. However, is the C7 SP always longer and more prominent, or is there a deviation from this morphology? The purpose of this study was to answer the question above. A total of 195 subjects were included in this study: 93 men (47.7%), with a mean age of 42.14 years, and 102 women (52.3%), with a mean age of 49.43. The length of the SP was determined to be the middle point of the SP’s origin, from the vertebral lamina up to the middle of its tip. The comparisons of continuous variables were done by the t-test, using the SPSS 20.0 package. In males, C7 SP is longer in 72.90% and T1 is longer in 27.1% ; in females, C7 is longer in 42.7% and T1 is longer in 57.3% , respectively. Therefore, there is a statistically significant difference of C7 – T1 SP morphology. In males, the average length of C7 SP was 44,11 mm ; in females, the average length of C7 SP was 37,82 mm . In males, the T1 SP length was 47,93 mm ; in females, the T1 SP length was 40,44 mm . The anatomical differences of C7 and T1 SP lengths are now described qualitatively and quantitatively in a Mediterranean population sample. It is found that there is a sexual dimorphism, with C7 SP in the males and T1 in females often being longer. The morphological patterns found in this study vary from those published earlier about scoliotic subjects, a finding that may implicate SP morphology in idiopathic scoliosis aetiology. Based on these results, the necessity of finding the correct anatomical landmark on the surface of the torso (SPs of C7 or T1) is confirmed for the purpose of clinical examination and for surface topography apparatus to correctly function in a scoliosis clinic. In addition, finding the correct anatomical landmark on the torso is essential to a number of other medical specialties using surface anatomical landmarks .


Hearing aid technology has improved dramatically in the last decade, especially in the ability to adaptively respond to dynamic aspects of background noise. Despite these advancements, however, hearing aid users continue to report difficulty hearing in background noise and having trouble adjusting to amplified sound quality. These difficulties may arise in part from current approaches to hearing aid fittings, which largely focus on increased audibility and management of environmental noise. These approaches do not take into account the fact that sound is processed all along the auditory system from the cochlea to the auditory cortex. Older adults represent the largest group of hearing aid wearers; yet older adults are known to have deficits in temporal resolution in the central auditory system. Here we review evidence that supports the use of the auditory brainstem response to complex sounds (cABR) in the assessment of hearing-in-noise difficulties and auditory training efficacy in older adults. In recent years, scientists and clinicians have become increasingly aware of the role of cognition in successful management of hearing loss, particularly in older adults. While it is often said that “we hear with our brain, not just with our ears,” the focus of the typical hearing aid fitting continues to be one of providing audibility. Despite evidence of age-related deficits in temporal processing –6, abiliThe cABR provides an objective measure of subcortical speech processing , 13. It The cABR is recorded to alternating polarities, and the average response to these polarities is added to minimize the cochlear microphonic and stimulus artifact , 19. PhaF0), and timbre (the integer harmonics of the F0) . Pe. PeF0 af voices ; therefose group . These rthe cABR . Furtherthe cABR  found thThe cABR provides evidence of age-related declines in temporal and spectral precision, providing a neural basis for speech-in-noise perception difficulties. In older adults, delayed neural timing is found in the region corresponding to the CV formant transition , 60, butWhat is the role of the cABR in clinical practice? The cABR can be collected in as little as 20 minutes, including electrode application. Nevertheless, even an additional twenty minutes would be hard to add to a busy practice. To be efficacious, the additional required time must yield information not currently provided by the existing protocol. One of the purposes of an audiological evaluation is to determine the factors that contribute to the patient's self-perception of hearing ability. To evaluate the effectiveness of possible factors, we used multiple linear regression modeling to predict scores on the speech subtest of the Speech, Spatial, and Qualities Hearing Scale . Pure-toF0 to a target sound presented in a noisy background than their age-, sex-, and IQ-matched monolingual peers. Within the bilingual group, a measure of sustained attention was related to the strength of the F0; this relation between attention and the F0 was not seen in the monolingual group. Krizman et al. [F0.As the site of intersecting afferent and efferent pathways, the inferior colliculus plays a key role in auditory learning. Indeed, animals models have demonstrated that the corticocollicular pathway is essential for auditory learning , 64. Then et al.  proposedMusicianship, another form of auditory expertise, also extends to benefits of speech processing; musicians who are nontonal language speakers have enhanced pitch tracking to linguistically relevant vowel contours, similar to that of tonal language speakers . Ample eMusicians' responses to the cABR are more resistant to the degradative effects of noise compared to nonmusicians , 73. BacBut, what about the rest of us who are not able to devote ourselves full time to music practice—can musical training improve our auditory processing as well? Years of musical training in childhood are associated with more robust responses in adults , in thatF0 of the stimulus, and changes in phase locking were related to changes in behavioral thresholds.Short-term training can also engender subcortical plasticity. Carcagno and Plack  found chF0 and decreases in the number of pitch-tracking errors [Just as long-term exposure to tonal language leads to better pitch tracking to changing vowel contours, just eight days of vocabulary training on words with linguistically relevant contours resulted in stronger encoding of the g errors . The parTraining that targets speech-in-noise perception has also shown benefits at the level of the brainstem . Young aThere is renewed clinical interest in auditory training for the management of adults with hearing loss. Historically, attempts at auditory training had somewhat limited success, partly due to constraints on the clinician's ability to produce perceptually salient training stimuli. With the advent of computer technology and consumer-friendly software, auditory training has been revisited. Computer technology permits adaptive expansion and contraction of difficult-to-perceive contrasts and/or unfavorable signal-to-noise ratios. The Listening and Communication Enhancement program  is an example of an adaptive auditory training program that employs top-down and bottom-up strategies to improve hearing in noise. Older adults with hearing loss who underwent LACE training scored better on the Quick Speech in Noise test (QuickSIN)  and the F0 in response to speech sounds presented in noise but not in quiet. Importantly, the amplitude of the F0 at pretest predicted training-induced change in speech-in-noise perception. The advantages of computer-based auditory training for improved speech-in-noise perception and neural processing have also been observed in older adults [The benefits on the HINT and QuickSIN were replicated in young adults by Song et al. . After cr adults . Based oAny clinician who has experience with fitting hearing aids has encountered the patient who continues to report hearing difficulties, no matter which particular hearing aid or algorithm is tried. Although we have not yet obtained empirical evidence on the role of the cABR in the hearing aid fitting, we suggest that implementation of the cABR may enhance hearing aid fittings, especially in these difficult-to-fit cases. The clinician might be guided in the selection of hearing aid algorithms through knowledge of how well the brainstem encodes temporal and spectral information. For example, an individual who has impaired subcortical timing may benefit from slowly changing compression parameters in response to environmental changes.We envision incorporating the cABR into verification of hearing aid performance. Cortical-evoked potentials have been used for verifying auditory system development after hearing aid or cochlear implant fitting in children –89. In aWith improvements in digital hearing aid technology, we are able to have greater expectations for hearing aid performance than ever before, even in noisy situations . These i


This paper describes the design, development, and tests of a low cost ALS. It was designed for hearing-impaired student classrooms. It utilised digital wireless technology and was aimed to be an alternative to a popular FM ALS. Key specifications include transmitting in 2.4 GHz ISM band with eight selectable transmission channels, battery operated and chargeable, pocket size, and ranged up to thirty metres. Audio characteristics and user tests show that it is comparable to a commercial system, currently employed in our partner school. The results also show that wearing an ALS clearly improves hearing of hearing-impaired students. Long-term usage by school children will be monitored to evaluate the system robustness and durability. Assistive listening systems (ALSs) are devices that help hearing-impaired people, by reducing the effects of ambient noise and distance on sound travel. Sound progresses from a source, such as a speaker, through air to listener's ears. During travel, sound quality deteriorates. Longer distance reduces amplitude, and surrounding noise interferes with the original sound. This combination causes hearing difficulty to normal listeners, and the effects are more significant to hearing-impaired people.An ALS generally consists of a transmitter and a receiver. The transmitter picks up sound near the source, usually by a microphone. It then converts it into electronic signal. The signal is transmitted to the receiver through wires, or by wireless transmission protocols. The receiver sends the signal directly to a hearing aid or converts it back to sound for the user. Since the signal is transmitted electronically, the adverse effects of distance and background noise are eliminated. The sound quality that a listener hears is close to the sound quality from the sound source. Hence, an ALS essentially maintains a signal-to-noise ratio (SNR) of the sound source. ALS could be used together with a hearing aid. The hearing aid function is to amplify the sound to compensate for a user's hearing impairment.A hearing-impaired person has difficulty differentiating the sound source from surrounding noises . ALS helSignal transmission between transmitter and receiver through wire obviously limits ALS practical use and portability. Personal ALSs, therefore, rely on wireless transmission. Current ALSs employ one of these three technologies: induction loop (IL) , infrareOf the three systems, FM is the most popular. The sound signal is frequency modulated onto a radio-frequency carrier wave. The wave is sent from a transmitter to a receiver, which is set to the same frequency. The receiver then demodulated the carrier wave to retrieve the original sound signal. The technology is the same as radios, where radio stations are transmitters and household radios are receivers. The original sound signal can reach the user by earphone, headphone, or through a hearing aid via a neckloop or digital audio input (DAI) connector. An example FM system from Williams Sound Corporation is shown in FM systems were initially employed in broadcasting applications, such as in classrooms for hearing-impaired students . CurrentAs with FM radios, FM ALSs have to operate within approved frequency bands. The United States Federal Communications Commission (FCC) allocated 72–76 MHz frequency band for ALS usage. Subsequently, 216-217 MHz was also allowed for ALS. However, there is no specific frequency band for ALS globally. FM ALS has advantages over the IL system in terms of lower transmitting power and longer range. It also requires no line of sight between transmitter and receiver, as compared to IR. However, FM ALSs can be subject to signal interference and bad reception. FM radio users probably have experienced similar problems, which adversely affect sound quality. For the above reasons, this paper describes our development of a low-cost wireless ALS broadcasting system. The system utilises a wireless digital technology communication. It operates in a 2.4 GHz unlicensed industrial, scientific, and medical (ISM) radio band. The internationally unrestricted ISM band allows the system to operate in most countries. Due to the band-wide ranging applications, ISM-based components are readily available and at low costs. Furthermore analogue FM signal could be digitally processed to reduce noise and improve signal quality. The system is designed to be short ranged and in one-to-many broadcasting mode. It is intended to be used in a classroom for the hearing-impaired students. This paper is organised into four sections. This project has produced three previous versions of the system, before achieving the final set. The earlier versions were assembled on development boards, temporary boxes, and field cases. The assembly and test results were reported in . The anatransmits in broadcast mode at 2.4 GHz,uses chargeable battery that lasts at least 4 hours ,is chargeable via portable charge switching (same as mobile phone charging),can work with both internal and external microphones,has eight selectable frequency channels,has working range of up to 30 metres,has to fit into a shirt pocket and could be tucked onto a belt.For practical classroom of the hearing-impaired usage, the system was designed to meet the following specifications:As mentioned earlier, the 2.4 GHz is the international frequency band, allocated for scientific and medical usage. A device can transmit in this band without having to seek government permission. The partner school currently uses commercial FM systems. Teachers carry transmitters and students carry receivers with them during class. Students return their devices to teachers during lunch and at the end of school day for charging. Hence, the specifications are designed to meet their usage, in terms of ease of charging and battery life.In class, teachers speak into an external microphone which is connected to the transmitters. However, internal microphone was added to the specification for flexibility of usage. For example, a transmitter can be placed in front of a television or radio. In this case, an external microphone would not be needed.Selectable frequency channels were included to avoid interference from nearby classrooms. When interference occurs, a teacher can tell all students to switch to different channels. Normal classroom length is six to eight metres. The 30-metre operating range is placed in the specifications to meet a teacher's suggestion that it should be long enough to cover outdoor class.For practical purpose, the system has to be portable. Students put them in their shirt pockets, and teachers tuck them on their belts; so our system size was designed to meet this requirement.From the above specifications, the system architecture was designed as shown in The signal from a condenser microphone was modified with an analogue amplifier circuit. The amplified signal was sent to a dsPIC33FJ128GP708A 16-bit low power microcontroller [The power management circuit consisted of analog charging circuit and the 1.2 V and 3.3 V regulator circuits.The receiver module is shown in The receiving circuit board contained the same microprocessor and microcontroller as the transmitting circuit board. They performed the reverse tasks, by basically selecting the channels and demodulating signal. Before reaching a listener, the signal was improved by filtering noise and amplified. Filtering was done by a simple low pass filter. The amplifier circuit output was adjusted by user rolling switch. The user could then select desirable output volume. The power management circuit was the same as in the transmitter.Since the system was designed for actual usage by primary school children, robustness and durability were the main concerns. All the circuits were integrated into a single two-sided printed circuit board (PCB). Moderately thick PVC casing was used to house the assembly. The case had width, length, and thickness 2.7 centimetres, 7.8 centimetres, and 2.7 centimetres, respectively. The transmitter and receiver PCBs are shown in Performance characteristics and user tests were done on the system to evaluate its performance. The system was tested for three key performance characteristics prior to the field test on users. They were the full-on gain, measured via HFA FOG 50 dB setup following IEC60118-7 standard, total harmonic distortion (THD), and its audio bandwidth. These parameters would help us determine the quality of audio signal produced, as the ALS was designed with a built-in amplifier. Full-on gain will tell us the amplification gain, bandwidth the range, and THD the quality of the signal.  The test was done using the software “Sound Check 8.1” and Anechoic Test Box Type 4232. The transmitter was placed in the box next to a speaker, which played a sound at different test frequencies. The receiver was placed next to the box. The received signal from the receiver was passed on to the box microphone. The signal picked up from the microphone was sent to the software for evaluation. The experiment setup is shown in The software calculated HFA FOG 50 dB, which is the high frequency average gain given input at 50 dB, audio bandwidth, and total harmonic distortion (THD). The HFA FOG 50 dB was 67.3 dB. The audio bandwidth was the range between low and high frequency cutoffs. Our ALS had the bandwidth of 133 Hz–6.52 kHz. THD was measured at three different input frequencies. At the input of 500 Hz and 70 dB (SPL), THD was 11.8%. At the input of 800 Hz and 70 dB (SPL), THD was 13.3%. At the input of 1,600 Hz and 65 dB (SPL), THD was 2.5%. Reading from the results, it can be seen that the ALS has a gain of 67.3 dB, which is considerably high as intended, comparable to the rage of hearing aid amplification needed for user with moderate-to-severe hearing loss. The bandwidth achieved also covers the targeted speech rage. In terms of THD, the values are relatively high compared to the range of 1-2% expected from hearing aids, but still competitive compared to THD of FM products available in the markets that we also measured. This implies that the quality of the audio signal would be between that of hearing aids and commercial FM products.The field test was designed to test our ALS in an actual operating environment which was in classrooms of hearing-impaired students. It was also tested by prospective users, which were the hearing-impaired students from our partner school. In the test, students would listen to separate Thai words and write them down. The results would reflect their ability to hear and recognise words when using ALS.It was carried out in the school library. The recorded words were played from a speaker. The testers sat 10 metres away from the speaker. The library was used because available classrooms were 8 metres long, which were shorter than our ALS specifications.Five students participated in the test. All of them had severe 71–90 dB HL) to profound (91+ dB HL) levels of hearing loss of both ears [0 dB HL tThree sets of 25 phonetically balanced (PB) Thai words were used, one for each test.Each word was played three times. Students would pronounce the word they hear and write it down.Each student was accompanied by an observer who would listen and note down the words each student said. This was because students may have limited spelling skills. They might have heard the word correctly but spelt it wrongly. The observers' notes would be used for analysis.The order of word sets and devices used was randomly set for each student.During the test, SNR was measured to be between 10 and 15.Classification of hearing correctness was listed as follows:correct absolutely (whole word);correct only for the first syllable and vowel. English equivalent example of this case would be hearing “pass” instead of “past”;correct only for the first syllable. English equivalent example of this case would be hearing “cat” instead of “cow”;correct only for the vowel. English equivalent example of this case would be hearing “can” instead of “bat”;Class teachers would remove the words, perceived to be unknown to individual students from the result.For comparison, each student would do three identical tests but using three different devices. They would wear our ALS, a commercial FM ALS currently used in the school, and their own hearing aids with no ALS. The test details were as follows.The experiment was shown in (a) Field Test Results. The raw results for individual students are shown in (b) Field Test Result Analysis. From It should be noted that hearing performance of students when wearing either our or school ALS is nearly twice as much as when not wearing ALS. The result supports the obvious benefit of ALS to hearing-impaired people. At 10 metres, original audio signal deteriorates so much that makes hearing difficult. ALS helps transmit signal while maintaining quality close to the original signal.It can be seen from The notes from the observers are not reported here, because the observers were mostly unable to recognise the words that students pronounced. It is observed that only skillful listeners such as teachers could understand individual students' speech.In this work, we describe the development of a low cost wireless broadcasting ALS. It was designed for short-range application, such as in the classroom for the hearing-impaired students. The results from audio characteristics and field test, by prospective users, suggest that its performance is comparable to an existing ALS system. It is hence a viable alternative to existing FM ALS. The ALS was also designed to address another practical issue commonly faced when students usually found using hearing aids that are incompatible with existing ALS , making them either not using the ALS or using it without the hearing aid. The ALS in this project was designed with a built-in amplifier to help the students to have the choice of using ALS alone without completely losing hearing aid's amplification benefits. The built-in amplifier was shown to have a gain of 67.3 dB, a level that can be useful for students with moderate-to-severe hearing loss, with the bandwidth that can appropriately support speech communication. The bill of materials of the system costs approximately 150 US dollars for each transmitter or receiver. Our system costs several times less than the commercial FM ALS currently used in our partner school.Our ALS exceeds initial power target of lasting for four hours. It contains one 3.7 V 1000 mA lithium ion battery. When fully charged, it can operate up to ten hours. In school usage, students can wear them in class all day, and the teachers can charge them overnight.The 2.7 cm × 7.8 cm × 2.7 cm dimension makes our ALS fit into student's shirt pocket or snap to teacher's belt comfortably. Each unit weighs just over 100 grams. We anticipate that it could be made lighter, by changing plastic material for casing. The current material is PVC which is strong but heavy.We are in the process of assembling a set of two transmitters and ten receiver units. They would be given to our partner school for long-term use. We plan to keep usage and maintenance record for at least six months. This should provide data of our ALS robustness and durability, which is our main concern. From observation there seems to be much wear and tear with children users. Furthermore, there are additional chances of the system being accidentally exposed to moisture and water. This would severely test our system robustness and durability.


We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI) revealed bilateral enlargement of the endolymphatic sacs of the inner ear. With improved cooperation, audiometric testing showed that hearing loss was most profound on the right, where endolymphatic sac enlargement was greatest, demonstrating a clear link between the degree of deafness and the degree of inner ear abnormality. This case indicates the value of MRI for diagnosis of inner ear involvement in very young children with distal RTA. Although citrate therapy quickly corrects the acidosis and restores growth, early diagnosis of deafness is crucial so that hearing aids can be used to assist acquisition of speech and to provide enough auditory nerve stimulation to assure the affected infants remain candidates for cochlear implantation.Hereditary distal renal tubular acidosis (dRTA) is caused by mutations of genes encoding subunits of the H Several hereditary forms of dRTA are caused by mutations in genes that encode the tubular transporter linked to distal hydrogen ion excretion. Specific missense mutations of the Clhanger AE gene  can be found in a variety of different etiologies for hearing loss in children . In dRTARecognition of primary dRTA is fairly straightforward for the pediatric nephrologist, since affected children have alkaline urine and absence of urinary ammonium ion, despite systemic acidosis. However, in infants, it may be difficult to determine whether there is associated sensorineural deafness and whether hearing loss is severe. This is a crucial issue, since it may prompt early hearing aid intervention and preserve enough auditory nerve function to make eventual cochlear implantation worthwhile. We report the case of a young girl with dRTA who is compound heterozygous for one known and one novel mutation in the ATP6V1B1 gene in whom inner ear involvement was initially uncertain but was firmly demonstrated by endolymphatic sac dilatation visible on magnetic resonance imaging. In this case the endolymphatic sac is clearly more enlarged on the side that has the more severe hearing loss. A 17-month-old girl was admitted to the Montreal Children's Hospital because of failure to thrive over the previous five months. She was the first child of a nonconsanguineous couple, the father of Greek descent and the mother of French Canadian origin. The parents reported that she often appeared thirsty and woke up in the night to drink, soaking 6–8 diapers per day. She was not tolerating solid foods well but had no chronic diarrhea.z-score −3.2) and height was 77 cm (z-score −0.88). Her development was significantly delayed; she was barely able to sit and was unable to walk. She made only babbling sounds, was very irritable, and did not interact normally with others. Her weight was 7.940 kg (+ = 2.6 mmol/L). Other serum values included: sodium = 133 mmol/L, chloride = 108 mmol/L, calcium = 2.46 mmol/L, phosphate = 1.3 mmol/L, creatinine = 45 μmol/L, and normal PTH (3.9 pmol/L). Red blood cell morphology was normal, but urine pH  (7.5) was inappropriately high. There was no evidence of proteinuria or glucosuria, and tubular reabsorption of phosphate (81%) was only marginally decreased. Laboratory testing revealed a normal anion gap metabolic acidosis (bicarbonate = 14.7 mmol/L) with hypokalemia  positive urinary anion gap (UAG = U+Na + U+K − U−Cl) indicating absence of ammonium ion; (C) correction of serum bicarbonate from 18.8 to 20.6 meq/L with 1 mmol/kg NaHCO3 . Distal RTA was confirmed by: (A) abnormally low urine minus plasma pCOg NaHCO3 . Her reng NaHCO3 . ATP6V1B1 exons and identified a putative pathogenic mutation on each allele (IVS7 + G > T/p420fs434X). Although distal RTA was thought to explain her failure to thrive, her developmental delay was initially attributed to a familial form of autism since this diagnosis had been made in a maternal cousin and initial audiometry was inconclusive because of poor cooperation. However, cerebral magnetic resonance imaging revealed marked enlargement of the endolymphatic sac bilaterally. On the right, the sac measured 15 × 19 mm in transverse and craniocaudal dimensions, respectively . Subsequz-scores of −1.12 (13% ile) by 2 years of age. Following interventions by the speech therapist, gross motor milestones, socialization, and speech have improved.The patient started oral potassium citrate therapy (3 mmol citrate/kg per day). Her acidosis and hypokalemia resolved over the next 6 months, and she had good catch-up growth reaching weight Our patient presented with typical clinical signs of distal RTA, and further testing confirmed a defect in distal hydrogen ion secretion. However, her family history had led to a preliminary diagnosis of autism rather than deafness. Initial audiometry at 17 months of age was uninterpretable because of poor cooperation. Surprisingly, magnetic resonance imaging revealed dilatation of the endolymphatic sacs on both sides and clearly identified a primary pathology in the middle ear. Enlargement of the endolymphatic sacs has been reported in association with other forms of sensorineural hearing impairment, but in most (84%) there are coexistent cochlear and/or vestibular anomalies  (not preGenetic testing showed that the patient was a compound heterozygote for a novel mutation (c.1259insT) and a previously described mutation (c.687 + 1G > T) in the ATP6V1B1gene . The c.1+ATPase mutations and to gauge the local extent of inner ear damage. This is particularly important since cochlear dysfunction is progressive and is not reversed by the alkali therapy that corrects distal RTA. Affected children with residual hearing may benefit by early hearing aid intervention to optimize acquisition of speech and to assure ongoing stimulation of the auditory nerve. This may maximize the success of subsequent cochlear implantation at a later time.Interestingly, our patient had severe dilatation of the right endolymphatic sac, where there was no apparent hearing below 80 decibels. Endolymphatic sac dilatation was significantly less on the left side where there was still some residual hearing. Thus, magnetic resonance imaging may be useful in dRTA both to identify the inner ear pathology associated with H


Surfactant protein A (SP-A), encoded by two functional genes, SP-A1 and SP-A2, is essential for the inflammatory process and host defence in the lungs. Recent studies have demonstrated the extrapulmonary expression of SP-A. Similar to the lungs, the kidneys are organs exposed to external pathogens. The present study evaluated the expression and location of SP-A in the kidneys. The effect of lipopolysaccharide (LPS) on the expression of SP-A subtypes was also studied in renal tubular epithelial (HK-2) cells.Immunohistochemical staining was performed using polyclonal antibody against SP-A. RT-PCR was also performed using mRNA from normal human renal tissues and HK-2 cells. The expressions of the SP-A1 and SP-A2 genes were determined by PCR-based RFLP analysis, gene-specific amplification, and direct sequencing of RT-PCR products. Western blot was conducted to analyse the SP-A protein. HK-2 cells were treated with LPS at various concentrations  for 8 h and at 5 μg/mL at various time points . The LPS-induced expressions of SP-A1 and SP-A2 mRNA and protein were analysed by RT-PCR and Western blot.P < 0.05).SP-A was localised in the renal tubular epithelial cells in the proximal and distal convoluted tubules. SP-A1 and SP-A2 mRNA and protein were expressed in HK-2 cells and human renal tissues, which were significantly increased in time- and dose-dependent manners after LPS treatment (Human renal tubular epithelial cells can express both SP-A1 and SP-A2 genes, which may play important roles in the inflammatory modulation of the kidney. Pulmonary surfactant, a complex mixture of lipids and proteins, is produced and secreted by alveolar type II cells . ApproxiSP-A participates in the pathophysiological and physiological regulation of the inflammatory process in the lungs . SP-A caIn the present study, we determined whether SP-A1 and SP-A2 mRNA and proteins are expressed in human renal tissues and HK-2 cells. We also evaluated the effects of LPS on the regulation of SP-A subtype expressions in HK-2 cells.Human renal tissue samples obtained from 10 patients  who underwent operations for renal cancer were used in the present study. Furthermore, lung tissue samples were obtained from five patients who underwent operations for lung cancer . The experimental procedure was carried out according to the protocol approved by the Human Ethics Committee of the Renmin Hospital of Wuhan University in China.2 and then treated with Dulbecco’s modified Eagle’s medium  in a mixture of 10% foetal bovine serum  and 1% ampicillin. The culture medium was changed every 2 d until the cells reached 70% to 80% confluency, at which point they were dissociated with 0.25% trypsin/EDTA. Subsequently, the cells were incubated for 24 and 72 h to determine mRNA and protein expressions, respectively.Renal tubular epithelial cells  were cultured at 37°C in a humidified atmosphere of 5% CO2O2 in methanol for 30 min at room temperature to inhibit endogenous peroxidase activity, they were incubated with a primary antibody  at 4°C overnight. The sections were washed in phosphate-buffered saline (PBS) repeatedly and then incubated with an anti-rabbit secondary antibody conjugated with horseradish peroxidase. Negative controls were stained with PBS instead of the primary antibody. Slides were rinsed in PBS and then incubated in diaminobenzidine chromogen . Colour development was observed under a microscope. The slides were counterstained with haematoxylin to determine the presence of nuclei.Human renal tissues were embedded in paraffin (4 μm thick) and then immunohistochemically examined using a SP-A polyclonal antibody (supported by Prof. Guirong Wang ). After Normal human renal tissues and cultured HK-2 cells were used for RT-PCR analysis of SP-A and GADPH mRNA, and alveolar tissues were used as positive controls. An oligonucleotide dT primer and primer pairs of the target and control genes, respectively, for RT-PCR were purchased from Invitrogen Corporation Table . Total RApproximately 10 μL of the PCR product  was digested using 2 μL of the restriction enzyme Apa I , 2 μL of 10× buffer B, and 18 μL of double-distilled water at 37°C for 12 h. The treated PCR product (8 μL) was then electrophoresed on 2% agarose gel.Another PCR product  was subjected to electrophoresis on 2% agarose gel and then purified using a TIANgel Midi purification kit  according to the manufacturer’s instructions. Sequencing was then directly performed using an ABI 3730xl 96-capillary DNA analyser.Proteins from human tissues (kidneys and lungs) and HK-2 cells were extracted using RIPA lysate . The total protein concentrations were determined using the bicinchoninic acid protein assay (Hyclone Pierce). Total protein (50 μg) was resolved by reducing 12% SDS-polyacrylamide gel electrophoresis and then transferred electrophoretically at 60 mA onto nitrocellulose membranes at 4°C overnight . After the samples were blocked in 5% non-fat milk in Tris-buffered saline, immunoblotting was detected using a primary antibody against SP-A and a anti-rabbit secondary antibody conjugated with horseradish peroxidase. Cellular β-actin protein was immunodetected using a human monoclonal antibody against human β-actin (Sigma) as the internal standard. Immunoproducts were detected using enhanced chemiluminescence peroxidase detection reagents .Escherichia coli 0111:B4 (Sigma) for 8 h and then with 5 μg/mL of LPS at different time points . The cells were collected to detect the expressions of SP-A1 and SP-A2 mRNA and SP-A protein as described above.HK-2 cells were incubated with various concentrations  of LPS from Data were expressed as mean ± SEM. Results were analysed using one-way ANOVA with SPSS 13.0 software. P < 0.05 was considered to indicate statistical significance.The immunohistochemical experiment using a specific SP-A antibody revealed the localisation of SP-A in the paraffin sections of renal tissues n = 10). SP-A  were amplified from the renal tissues and HK-2 cells  was analysed through direct sequencing to identify whether SP-A is transcribed from one or both SP-A genes in the HK-2 cells. The sequencing results in Figure Western blot analysis of human renal tissues and HK-2 cells showed bands at approximately 33 kDa. The expression levels of SP-A were decreased compared with those in the lungs, as illustrated in Figure The effects of LPS on SP-A1 and SP-A2 mRNA and protein syntheses were determined by RT-PCR and western blot analysis. In the untreated cells, the expressions of SP-A1 and SP-A2 mRNA and protein were detected Figure . The HK-The present study demonstrated the expression and localisation of SP-A within the renal tissue. LPS selectively induced the expressions of SP-A1 and SP-A2 mRNA and protein in human tubular epithelial-like HK-2 cells in time- and dose-dependent manners.Although the bands for SP-A (33 kDa) in the kidney extracts were detected by Kankavi , SP-A mRBoth SP-A1 and SP-A2 transcripts are expressed in adult human alveolar type II cells . McCormiE. coli. Thus, the severity and time course of kidney inflammation may depend on the amount of LPS. SP-A is the most abundant surfactant protein in the lungs and contributes to lung host defence. A previous study reported that SP-A gene knocked-out mice are susceptible to lung infection caused by several pathogens. In the present study, the levels of SP-A1 and SP-A2 mRNA and protein in the HK-2 cells were significantly increased after LPS treatment. This finding indicated that SP-A may play an anti-inflammatory role in kidney infection.In the present study, we have shown that both SP-A1 and SP-A2 mRNA is expressed in renal tissue and the HK-2 cell line. As the SP-A protein can be detected by the polyclonal antibody of SP-A as well in renal tissue and the HK-2 cell line, as shown by western blotting and immunohistochemistry, the polyclonal antibody could potential recognise epitopes in both the SP-A1 and SP-A2 proteins. Therefore, the localisation and synthesis of SP-A occur in the kidneys. Immunostained SP-A is present in the epithelial cells of different tissues, such as in the Eustachian tube  and nasaIn summary, the following conclusions are presented. First, human renal tubular epithelial cells can transcribe both SP-A1 and SP-A2 genes. Second, LPS induces SP-A1 and SP-A2 mRNA and protein syntheses in time- and dose-dependent manners. Third, SP-A in the renal tissues may prevent the spread of specific infections from the urinary tract to other body parts. However, the mechanism should be further studied.In summary, human renal tubular epithelial cells can express both SP-A1 and SP-A2 genes, which may play important roles in the inflammatory modulation of the kidney.SP-A: Surfactant proteins A; LPS: Lipopolysaccharide; TNF-α: Tumor necrosis factor-α; IL-1: Interleukin-1; DAB: Diaminobenzidine.The authors declare that they have no competing interests.JL carried out the cell incubation experiment, SP-A1/SP-A2 detection and drafted the manuscript. FQH carried out the SP-A1/SP-A2 expression induced by LPS. GRW participated in the design of the study. QSZ performed the statistical analysis. GHD conceived of the whole study, participated in its design and coordination. All authors read and approved the final manuscript.


Objective. This study assessed the posttreatment tumor control and auditory function of vestibular schwannoma (VS) patients after CyberKnife (CK) and analyzed the possible prognostic factors of hearing loss. Methods. We retrospectively studied 117 VS patients, with Gardner-Robertson (GR) classification grades I to IV, who underwent CK between 2006 and 2012. Data including radiosurgery treatment parameters, pre- and postoperative tumor size, and auditory function were collected and examined. Results. With CK, 117 patients had excellent tumor control rates (99.1%), with a mean imaging followup of 61.1 months. Excluding 52 patients (GR III-IV pretreatment), 53 (81.5%) of the remaining 65 patients  maintained GR I or II hearing after CK, with a mean audiometric followup of 64.5 months. Twelve patients experienced hearing degradation (91.6% were GR II pretreatment); they appeared to have significantly larger tumor sizes, significantly smaller cochlear sizes, and higher prescribed cochlear doses, compared to the patients with preserved hearing. Conclusion. Our data showed that CK treatment provided an excellent tumor control rate and a comparable hearing preservation rate in VS patients. Patients with pretreatment GR II hearing levels, larger tumor volumes, smaller cochlear sizes, and higher prescribed cochlear doses may have poor hearing prognoses. Vestibular schwannoma (VS) accounts for 6–10% of all brain tumors and is a histopathologically benign tumor, commonly arising from the sheath of cranial nerve VIII . When thOver the past few decades, stereotactic radiosurgery (SRS) is commonly used to treat patients with small VS tumors, with the primary goal of tumor control. There are several adaptations of SRS, such as gamma knife and, more recently, linear accelerator radiosurgery (LINAC). SRS has been shown to be an effective alternative to microsurgery for small- and medium-sized VS, with tumor control rates of 93–100% –12; howeThe CyberKnife (CK), which was first introduced by John Adler in 1994, is a dedicated robotic LINAC-based system, with the features of real-time image guidance, no rigid immobilization, and nonisocentric planning system . In otheThus, we performed this retrospective study to evaluate the tumor control, hearing outcomes, and possible prognostic factors of hearing loss in VS patients treated with CK, by using a fixed marginal dose of 1800 cGy in 3 sessions.This registry study was designed as a non-interventionist study in 2 medical centers in Taiwan, based on a therapeutic strategy and a retrospective patient chart review. The study was conducted in accordance with the Declaration of Helsinki-Good Clinical Practice. The protocol and study-related forms were both reviewed and approved by the Institutional Review Boards of the 2 medical centers in Taiwan.This retrospective chart review was performed for patients who had undergone CK for unilateral VS, between 2006 and 2012, excluding those with neurofibromatosis type 2, those without hearing (Gardner-Robertson classification [GR] V) [Dmax/prescribed dose, where Dmax  is maximum dose; CI = prescription isodose volume (PIV)/tumor isodose volume (TIV), where PIV is total 3D volume of the isodose line and TIV is tumor volume covered by the isodose volume; nCI = tumor volume (TV) × plan target volume (PTV)/(target isodose volume)2.Each patient was comfortably immobilized on the CyberKnife treatment table  and wore a custom-made Aquaplast mask . After an intravenous administration of 125 mL of Omnipaque contrast , a thin-slice high-resolution computed tomography (CT) and MRI T1 weighted image with contrast scan were obtained. Subsequently, the neurosurgeon outlined the tumor and its critical structures and generated a treatment plan with the CyberKnife Treatment Planning System (Multiplan v 2.1). Plans for CK treatment were evaluated using tumor coverage, homogeneity index (HI), conformity index (CI), and new conformity index (nCI). HI, CI, and nCI were calculated using the following formulas, respectively: HI =  3) = Tr(a × b × c)/6, where a, b, and c is width, height, and thickness, respectively [Baseline data, including patient characteristics  and treatment of VS (date of radiosurgery and prescribed dose) were collected. Pre- and posttreatment hearing results were measured, according to pure tone averages (PTA) and speech discrimination scores, and classified using GR classifications . Tumor sectively . When weectively , if the t test and Pearson Chi-square test were used to compare clinical parameters between groups, and a  P  value of <0.05 was considered statistically significant. Descriptive summaries were provided for the patients' demographics. The paired 3  and 42.5 mm3 , respectively. The mean duration of audiometric and imaging followups were 64.5 ± 17.3 months  and 61.1 ± 16.8 months , respectively.We reviewed the medical records of 117 patients ) with VS who had received CK between 2006 and 2012 . Fifty-sα/β = 3), with a 72–90% isodose line (mean 79.4%) and an average of 97.1% tumor coverage. Detailed cochlear dose-volume information is shown in 3.The tumors were irradiated with a marginal dose of 1800 cGy in 3 sessions, which is equivalently equal to 1130 cGy  (P < 0.001), significantly smaller cochlear sizes of 26.8 ± 13.8 mm3  (P < 0.001), and higher prescribed cochlear doses, with a maximum of 1525.7 ± 434.8 cGy  and a minimum of 919.3 ± 484.1 cGy . Overall, larger tumor volumes and small cochlear volumes were significantly associated with hearing losses after SRS.Of the 117 patients, 52 had nonserviceable or poor hearing (GR III-IV) pretreatment and were not counted in the following serviceable hearing preservation rates. As shown in After an average imaging followup of 61.1 months , tumor reductions were detected in 20 patients (17.1%), while the tumors remained unchanged in 96 (82.0%) patients. There is one patient who had tumor progression (0.9%), and therefore an overall tumor control rate of 99.1% was achieved. Surgical resection was once the traditional indication for VS. Today, however, continuous advancement in imaging technology and increased awareness of VS favor the early diagnosis of small- and medium-sized intracranial VS tumors. Therefore, the current management strategy for VS has shifted to observation, microsurgery, and radiation therapy, with an emphasis on the preservation of facial nerve function and hearing. Gamma radiosurgery, representing the gold standard in the SRS system, has been clinically proven to be effective in VS tumor control, but its hearing preservation rate, ranging from 55–79% , 22–26, Tumor control has been achieved in VS patients treated with SRS, including those with the CK system. Tumor control rates had reached 100% in 15 months , 98% in Aside from tumor control, hearing retention has been a substantial goal for CK treatment in VS. An early, small series reviewed 14 VS patients, initially with serviceable hearing (GR I or II) before CK, received mean marginal doses of 17 Gy in 1–3 sessions (prescribed dose 11.3 Gy). Thirteen of the fourteen cases retained serviceable hearing at the end of the followups, with functional hearing preservation rates of 93% . More re3 was a significant prognostic factor for serviceable hearing preservation. However, several articles suggested that a tumor's volume or diameter does not appear to be a risk factor for hearing loss after SRS for VS [3) had similar hearing preservation rates (62%) as those with larger tumors . As a whole, it remains difficult to draw a conclusion in terms of whether an increased tumor volume is a negative prognostic factor for functional hearing maintenance, owing to the diverse tumor volume thresholds chosen by researchers (0.75 cm3 versus 1.5 cm3) and the incomplete exclusion of possible influence from other tumor-related factors. First of all, tumor characteristics are targets of interest to researchers for improving hearing prognosis. Several factors, such as tumor location, intracanalicular tumor volume, entire tumor volume or diameter, and tumor growth rate, were investigated recently. Our study found that the patients who developed hearing degradation were characterized as having significantly larger tumor volumes than those of patients with preserved hearing, which was in agreement with the study by Kano et al.,  revealinS for VS , 28, 29.3 in patients who had their hearing preserved, which was nonsignificantly higher than those of patients with hearing degradation (80.4 mm3). More recently, a study, containing 94 VS patients treated with CK, had demonstrated that cochlear volume was positively associated with hearing preservation [In the present study, we showed that the patients who had diminished hearing after CK also had significantly smaller entire cochlear volumes those of patients with hearing preservation. The relationship between hearing preservation and cochlear volume has not yet been fully investigated. Massager et al.  reviewedervation , which rAccording to previous studies, a high radiation dose delivered to a cochlea is significantly associated with a worse hearing outcome , 30, 31.Observation is still a common treatment strategy for VS, especially for the elderly and those with small-sized tumors, owing to its noninvasive nature. However, there is increasing evidence for the benefits of early intervention. First, Yamakami et al.  systematSecond, as our data showed, 91.6% of the 12 patients experiencing hearing degradation after CK had a pretreatment hearing status of GR II, reflecting a greater probability of hearing loss in patients with GR II hearing pretreatment. Similarly, several articles showed that patients with GR I hearing prior to SRS have better hearing prognoses posttreatment , 33. ThiThis study had few limitations. Given that hearing loss after radiotherapy is a late effect and that VS generally grows slowly, our audiometric and imaging followups may not have been long enough, which may have resulted in a better hearing outcome and tumor control rate. Additionally, to some extent, it could be difficult to accurately measure the cochlear dose because the location and size of VS could influence the tumor coverage generated by the treatment planning system. Diversified cochlear structures also biased the estimation of radiation doses to proximal critical organs, which may result in inaccurate calculations of the radiation doses. In treating VS, possible treatments have achieved similar tumor control outcomes, so the toxicity profiles should be primarily considered when deciding on treatments. In addition to fractionating a course of radiation treatment, improving the targeting, accuracy, and conformity of the prescribed dose are known to be helpful in mitigating radiation toxicities , 17. TheThis study showed that VS patients receiving CK treatment achieved an excellent tumor control rate of 99.1%, with a comparable serviceable hearing preservation rate of 81.5%. Patients with posttreatment hearing deterioration were characterized as having GR II level hearing before CK, with larger tumor volumes and smaller cochlear sizes, and were prescribed higher doses to their cochleas. Overall, delivering 1800 cGy in 3 sessions by CK represents an effective and safe treatment option for the management of VS.


The present study investigates the hemispheric contributions of neuronal reorganization following early single-sided hearing . The experiments were performed on ten cats from our colony of deaf white cats. Two were identified in early hearing screening as unilaterally congenitally deaf. The remaining eight were bilaterally congenitally deaf, unilaterally implanted at different ages with a cochlear implant. Implanted animals were chronically stimulated using a single-channel portable signal processor for two to five months. Microelectrode recordings were performed at the primary auditory cortex under stimulation at the hearing and deaf ear with bilateral cochlear implants. Local field potentials (LFPs) were compared at the cortex ipsilateral and contralateral to the hearing ear. The focus of the study was on the morphology and the onset latency of the LFPs. With respect to morphology of LFPs, pronounced hemisphere-specific effects were observed. Morphology of amplitude-normalized LFPs for stimulation of the deaf and the hearing ear was similar for responses recorded at the same hemisphere. However, when comparisons were performed between the hemispheres, the morphology was more dissimilar even though the same ear was stimulated. This demonstrates hemispheric specificity of some cortical adaptations irrespective of the ear stimulated. The results suggest a specific adaptation process at the hemisphere ipsilateral to the hearing ear, involving specific (down-regulated inhibitory) mechanisms not found in the contralateral hemisphere. Finally, onset latencies revealed that the sensitive period for the cortex ipsilateral to the hearing ear is shorter than that for the contralateral cortex. Unilateral hearing experience leads to a functionally-asymmetric brain with different neuronal reorganizations and different sensitive periods involved. In developmental manipulations of the symmetry of auditory input, as occurs with unilateral deafness  cats were selected from a colony of deaf white cats using an early hearing screening procedure described earlier  show a specificity for the hemisphere. The cortex ipsilateral to the hearing ear demonstrates a functional shift toward the hearing ear  and the German Animal Welfare Act (TierSchG).To investigate developmental plasticity in animals with unilateral hearing, chronic stimulation by a cochlear implant was initiated at two different ages, reflecting the results of previous studies Figure :early , when the naive cortex shows a developmental peak in evoked synaptic activity , when synaptic activity in deaf animals fell below the level of hearing controls and the known sensitive period for aural preference has already expired  added to maintain a controlled depth of anesthesia  was infused i.v. The internal state was monitored by testing capillary blood every 12 h.For acute experiments, all animals were premedicated with 0.25 mg atropine i.p. and initially anaesthetized with ketamin hydrochloride  and propionylpromazine phosphate  or xylazine hydrochloride . The animals were then tracheotomized and artificially ventilated with 50% OThe animal's head was fixed in a stereotactic holder (Horsley-Clarke). Both bullae and ear canals were exposed. In order to record evoked auditory brainstem responses, a small trephination was drilled at the vertex and a silver-ball electrode (diameter 1 mm) was attached epidurally. Hearing status was tested at the beginning of the experiments. So as to prevent electrophonic responses, the hair cells in normal-hearing ears were destroyed by intracochlear instillation of 300 μl 2.5% neomycine sulphate solution over a 5 min. period and subsequent rinsing using Ringer's solution. The absence of hearing was subsequently confirmed by the absence of brainstem-evoked responses.Stimulation in the final acute experiments was performed using cochlear implants inserted bilaterally into the cochleae. In chronically electrically stimulated animals, the chronic implant was used for stimulation at the “hearing” ear. The stimulus was a biphasic pulse (200 μs/phase) applied through the apicalmost electrode contact at 10 dB above the lowest cortical threshold  that were moved along the auditory cortex with a micromanipulator (1 μm precision) at the cortical surface. Stimulus was 10 dB above the lowest cortical thresholds, the current level at which electrically-evoked LFPs reach the saturation point. By choosing that intensity the whole active volume of the cortex can be determined. The signals were amplified 5000–10,000 times, bandpass filtered (0.01–10 kHz), digitized (at a sampling rate of 25 kHz) and 50 responses were averaged to determine the mean LFP at each recording position. First, contralateral cortex was investigated, followed by the ipsilateral cortex. The tested combinations of recording site and stimulation site are shown in Table For recording, a trephination above the auditory cortex was performed and the dura was opened. First, within a grid of 3 × 3 positions, LFPs were recorded using low-impedance electrodes to determine the lowest cortical threshold for stimulation with a biphasic pulse (200 μs/phase) applied through the apicalmost electrode of the implant. Mapping of cortical responses was performed using glass microelectrodes . The signal before the response  was characterized by computing its mean and standard deviation. The threshold of mean ± 4Pa component, Figure t-test was carried out; if it failed, a Wilcoxon-Mann-Whitney test (both at 5% significance level) was used. Additionally, for each position a paired difference of the onset latency was computed. The medians were used as population measures since the latency values showed a significantly skewed distribution. Comparisons between the experimental groups were performed by applying the Wilcoxon-Mann-Whitney test .Using this measure, onset latencies were detected for the first positive response . Amplitudes below 50 μV were discarded from the processing to minimize the effect of noise on small amplitude signals.Peak amplitudes of t-test at α = 0.1%, adjusted to multiple comparisons using the false detection rate procedure  or born deaf and implanted at a later age . The ipsilateral cortex is the one on the same side of the brain as the hearing ear.In the present paper, the terms crossed” is used relative to the side of a given recording or stimulation and always refers to the “opposite” side of the brain. The term “uncrossed” refers to the same side as the ear stimulated or the cortex in which recordings were made.On the other hand, the term “Thus, if the left ear was the hearing ear, and a probe stimulus was presented at the right  ear, the crossed response refers to the response recorded at the left cortex and the uncrossed response refers to that at the right cortex. In this case, the ipsilateral cortex is then the left one and the contralateral cortex is the right one.Crossed and uncrossed responses compared at the same cortex tend to result in different LFPs in normal hearing animals, with crossed responses showing larger amplitudes and shorter latencies , more significant differences for the two stimulation sites were observed than at short latencies . For the crossed and uncrossed responses at the ipsilateral hemisphere, the LFP morphology was similar . However, comparing the crossed response of the contralateral hemisphere to the uncrossed response of the ipsilateral hemisphere resulted in larger difference . Further, crossed responses (compared between hemispheres) showed a high dissimilarity index of similar magnitude as the latter comparison . The dissimilarity index at the contralateral hemisphere for the crossed vs. uncrossed comparison was not different from the same at the ipsilateral hemisphere . Thus, interhemispheric comparisons resulted in larger DIs than intrahemispheric comparisons. Taken together, these results demonstrate that the cortical response shows hemispheric specificity in morphology irrespective of the ear that is stimulated. Although the largest DIs were found in the congenitally unilaterally deaf animal .To quantify this observation, dissimilarity index for s Figure . A Krusk Figures , the corA previous study demonstrated high plasticity of LFP onset latency and its sensitivity to developmental modifications  ear were compared between the cortices Figure . This cop = 0.044, Figure To verify this outcome, the difference in medians of uncrossed and crossed responses to the hearing ear was compared between early and late onset of asymmetric hearing Figure . In earlThe present manuscript describes hemispheric specificity of effects of unilateral hearing following congenital deafness. It demonstrates that in early-onset unilateral hearing, both the ipsilateral and the contralateral hemisphere reorganize and strengthen the responses to stimulation of the hearing ear, giving it an advantage over the deaf ear. In the early-onset animals, the ipsilateral hemisphere responded more strongly to stimulation of the hearing ear. The morphology of the LFPs demonstrated that the reorganizations following unilateral deafness were hemisphere-specific Figure .The uncrossed pathway appeared more susceptible to developmental alteration of hearing balance than the crossed pathway, although both the crossed and uncrossed responses to the hearing ear were changed by the stimulation. In late implantations, the uncrossed response did not show similar reorganization, and it was largely the crossed pathway of the hearing ear that still benefited from stimulation, although less than in early implanted animals Figures , 9. The The present study compared the effects of stimulation at both hemispheres. There are several limitations to the present approach that merit discussion. First of all, comparisons between hemispheres preclude pairwise testing. Although the present study used an approach validated by several previous studies performing interindividual comparisons  region of the cochlea within the first 2 years of life in congenitally deaf cats, and even at an older age there was less degeneration in the basal cochlea (Heid et al., Finally, age at final experiment did not significantly contribute to the present findings. The cortical developmental sequence in deaf and hearing cats with respect to electrically evoked responses terminates at ~6 months (Kral et al., Finally, it has to be considered that the effects measured at the ipsilateral cortex need not necessarily arise in the ipsilateral hemisphere, but may have an origin in the contralateral hemisphere before pathway crossing. For the sake of simplicity, however, we will not complicate the considerations below by including this aspect.The present study is well in agreement with previous investigations on the subject. The notion of auditory sensitive periods in neuronal plasticity (review in Kral, Early neonatal unilateral ablation studies suggested a reorganization of the auditory brain toward the hearing ear (Nordeen et al., The reorganization reported here and in previous studies is in accord with results from cochlear-implanted children (Peters et al., Importantly, the outcome shows specificity for the ear that has received input Figures , 4, 8. BSubcortical reorganization with deafness and cochlear implants has been described before (Snyder et al., The uncrossed response latency for stimulation of the hearing ear became smaller than the crossed response latency, so that the difference in medians was negative, but only in the early-implanted animals Figures , 10. ThiInhibitory synaptic transmission matures later than excitation (review in Kral et al., Stimulation of the hearing ear generates strong responses both at the ipsilateral and the contralateral hemisphere (for human data, see Bilecen et al., The present study supports the concept of several sensitive developmental periods by demonstrating a shorter sensitive period for reorganization at the ipsilateral hemisphere as compared with the contralateral hemisphere. It shows more extensive changes in uncrossed responses than in the crossed responses in early-onset animals. Furthermore, it shows that unilateral deafness results in an asymmetric brain, with different hemispheres showing differential responses for both the deaf and the hearing ear. The hemisphere ipsilateral to the hearing ear most likely downregulates inhibition, by that specifically decreasing onset latency of the response to the hearing ear. This effect is not found in the contralateral hemisphere.The deaf ear is, however, not completely ‘disconnected’ from the cortex following single-sided deafness. The hemisphere ipsilateral to the hearing ear preserves responsiveness to the deaf ear, although with a preference for the hearing ear. Finally, the present results support a greater ‘separation’ of the ears in early onset unilateral hearing.Dr. Jochen Tillein works also for MedEl Company, Innsbruck. His obligations in the company had no interference with the work nor is there any direct financial interaction between MedEl and the research performed in this study. The other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Magnetic resonance imaging (MRI) devices produce noise, which may affect patient's or operators' hearing. Some cases of hearing impairment after MRI procedure have been reported with different patterns . In this report, a case of bilateral sensorineural hearing loss in an otherwise healthy patient underwent brain MRI was described. The patient's hearing loss was accompanied with tinnitus and was not improved after 3 months of followup. Magnetic resonance imaging (MRI) usage as a diagnostic method is progressively increasing. Besides the advantages, MRI devices produce noise which may be hazardous for both operators and patients. It may cause such adverse effects as simple annoyance, anxiety, difficulty in verbal communication, changes in blood pressure and pulse rate, and temporary or permanent hearing threshold shift , 2.The main source of noise during MRI procedure is vibration produced by gradient magnetic field which reaches the auditory system. Despite substantial progressions in designing and the introduction of gradient coil, the need for high-speed MRI devices has led to the production of loud noise-generating devices .Our patient was a 29-year-old man with refractory headaches who has not responded to standard treatments; therefore, a brain MRI was indicated for him. The MRI was performed using a 1.5 Tesla Magnetom, Avanto device . During the 25-minute procedure, he did not use hearing protective equipment. One hour after the termination of the procedure, the patient felt tinnitus and hearing loss in his both ears. After two days, he was referred to our clinic without any considerable improvement in his symptoms. He did not complain of any other neurologic symptoms, such as blurred vision, sensory loss, or motor weakness.No history of exposure to loud noise, ototoxic drugs or substances, head trauma, metabolic abnormalities, and familial deafness was observed. He did not report to have had tinnitus or hearing loss ever before. The patient had been working as a truck driver for five years and was not a smoker or alcohol consumer. Of note, Rinne's test was positive which allowed us to rule out a conductive defect. In otoscopic evaluations, we failed to find any significant findings. Audiometry , tympanometry , and otoacoustic emissions (OAEs)  were also performed for him. As presented in As stated before, the main noise-producing element in MRI systems is rapidly alternating currents within the gradient coil of the system . StudiesPrice et al. have evaluated the noise produced by MRI scanners with different field strengths (from 0.2 to 3 Tesla). They reported the noise level to rise as the field strength increased (from 82.5 dB to 118.3 dB) . HoweverOur patient suffered from a bilateral mild sensorineural hearing loss after 25 minutes of exposure to noise from a 1.5 Tesla MRI device, which did not improve after 3 months. Similarly, de Wilde et al. reported a case of hearing loss accompanied with severe headache and dizziness after a 0.5 Tesla MRI without hearing protection . GovindaAccording to what Price et al.  have recThe United Kingdom Medical Device Agency has set limits for MRI noise exposure at a threshold of 85 dB (averaged over 8 hours) for patients and 90 dB (averaged over 8 hours) for operators. The agency recommends using HPDs above these limits . HPDs, iIn conclusion, MRI devices produce noise that may impair the hearing system of operators and patients with such symptoms as tinnitus, headache, ear pain, and dizziness. Consequently, preventive measures should be applied in cases that are planned to undergo off-limit exposures.


Then we introduce bifuzzy soft Lie subalgebras and investigate some of their properties.We introduce the concept of ( The concept of Lie groups was first introduced by Sophus Lie in nineteenth century through his studies in geometry and integration methods for differential equations. Lie algebras were also discovered by him when he attempted to classify certain smooth subgroups of a general linear group. The importance of Lie algebras in mathematics and physics has become increasingly evident in recent years. In applied mathematics, Lie theory remains a powerful tool for studying differential equations, special functions, and perturbation theory. It is noted that Lie theory has applications not only in mathematics and physics but also in diverse fields such as continuum mechanics, cosmology, and life sciences. A Lie algebra has nowadays even been applied by electrical engineers in solving problems in mobile robot control .bifuzzy sets. The elements of the bifuzzy sets are featured by an additional degree which is called the degree of uncertainty. This kind of fuzzy sets have now gained a wide recognition as a useful tool in the modeling of some uncertain phenomena. Bifuzzy sets have drawn the attention of many researchers in the last decades. This is mainly due to the fact that bifuzzy sets are consistent with human behavior, by reflecting and modeling the hesitancy present in real-life situations. In fact, the fuzzy sets give the degree of membership of an element in a given set, while bifuzzy sets give both a degree of membership and a degree of nonmembership. As for fuzzy sets, the degree of membership is a real number between 0 and 1. This is also the case for the degree of nonmembership, and furthermore the sum of these two degrees is not greater than 1.After introducing the concept of fuzzy sets by Zadeh  in 1965,γ, δ)-bifuzzy Lie algebra, and discuss some of its properties. Then we introduce bifuzzy soft Lie algebras and investigate some of their properties. We use standard definitions and terminologies in this paper.In 1999, Molodtsov  initiateIn this section, we review some known basic concepts that are necessary for this paper.Lie algebra is a vector space L over a field F  on which L × L → L denoted by → is defined satisfying the following axioms:(L1)x, y] is bilinear, = 0 for all x ∈ L,, z] + , x] + , y] = 0 for all x, y, z ∈ L (Jacobi identity)., z] = ]. But it is anticommutative; that is,  = −. A subspace H of L closed under  will be called a Lie subalgebra.Throughout this paper, μ be a fuzzy set on X; that is, a map μ : X → . As an important generalization of the notion of fuzzy sets in X, Atanassov introduced the concept of a bifuzzy set defined on a nonempty set X as objects having the formμ : X →  and ν : X →  denote the degree of membership ) and the degree of nonmembership ) of each element x ∈ X to the set A, respectively, and 0 ≤ μA(x) + νA(x) ≤ 1 for all x ∈ X.Let A =  be a bifuzzy set on X and let s, t ∈  be such that s + t ≤ 1. Then the sets, t)-level subset of A. As,t) on L is called a bifuzzy Lie subalgebra if the following conditions are satisfied: μA(x + y) ≥ min{μA(x), μA(y)},νA(x + y) ≤ max{νA(x), νA(y)},μA(αx) ≥ μA(x), νA(αx) ≤ νA(x),μ ≥ max{μ(x), μ(y)},ν ≤ min{ν(x), ν(y)}A bifuzzy set x, y ∈ L and α ∈ F.for all c be a point in a nonempty set X. If γ ∈  are two real numbers such that 0 ≤ γ + δ ≤ 1, then the bifuzzy set c = 〈x, cγ, 1 − cδ1−〉 is called a bifuzzy point (BP for short) in X, where γ  is the degree of membership  of c and c ∈ X is the support of c. Let c be a BP in X and let A = 〈x, μA, νA〉 be a bifuzzy set in X. Then c is said to belong to A, written c ∈ A, if μA(c) ≥ γ and νA(c) ≤ δ. We say that c is quasicoincident with A, written cqA, if μA(c) + γ > 1 and νA(c) + δ < 1. To say that c∈∨qA ∈∧qA) means that c ∈ A or cqA  ∈ A and cqA) and c∈∨qA does not hold.Let f and g be any two bifuzzy subsets of L. Then the sum f + g is a bifuzzy subset of L defined byLet U) denote the family of all bifuzzy sets in U.Let IF is called a bifuzzy soft set over U, where f is a mapping given by f : A → IF(U). A bifuzzy soft set is a parameterized family of bifuzzy subsets of U. For any ɛ ∈ A, fɛ is referred to as the set of ɛ-approximate elements of the bifuzzy soft set , which is actually a bifuzzy set on U and can beμfɛ(x) and νfɛ(x) are the membership degree and nonmembership degree that object x holds on parameter ɛ, respectively.Let f, A) and  be two bifuzzy soft sets over U. We say that  is a bifuzzy soft subset of  and write ⋐ if  (i)A⊆B, (ii)ɛ ∈ A, f(ɛ)⊆g(ɛ).for any Let  and  are said to be bifuzzy soft equal and write  =  if ⋐ and ⋐. and  be two bifuzzy soft sets over U. Then their extended intersection is a bifuzzy soft set denoted by , where C = A ∪ B andɛ ∈ C. This is denoted by Let  and  are two bifuzzy soft sets over the same universe U then “ AND ” is a bifuzzy soft set denoted by ∧ and is defined by ∧ = , where, h = h(a)∩g(b) for all  ∈ A × B. Here ∩ is the operation of a bifuzzy intersection.If  and  be two bifuzzy soft sets over U. Then their extended union is denoted by , where C = A ∪ B andɛ ∈ C. This is denoted by Let  and  be two fuzzy soft sets over a common universe U with A∩B ≠ ∅. Then their restricted intersection is a bifuzzy soft set  denoted by ⋓ = , where h(ɛ) = f(ɛ)∩g(ɛ) for all ɛ ∈ A∩B.Let  and  be two bifuzzy soft sets over a common universe U with A∩B ≠ ∅. Then their restricted union is denoted by ⋒ and is defined as ⋒ = , where C = A∩B and for all ɛ ∈ C, h(ɛ) = f(ɛ) ∪ g(ɛ).Let  and  over U is a fuzzy soft set, denoted by , where C = A ∪ B, and defined byɛ ∈ C. This is denoted by The γ, δ)-bifuzzy Lie subalgebra, and discuss some of its properties.In this section, we introduce a new kind of generalized bifuzzy Lie algebra, an  in L is called an -bifuzzy Lie subalgebra of L if it satisfies the following conditions: xγA,  yγA⇒(x + y), max)δA,xγA⇒(mx)δA,xγA,  yγA⇒, min)δAA bifuzzy set x, y ∈ L,  m ∈ F,  s, s1, s2 ∈ .for all xγA⇒(−x)δA,Consider (i) xγA⇒(0)δA.(ii) V be a vector space over a field F such that dim(V) = 5. Let V = {e1, e2,…, e5} be a basis of a vector space over a field F with Lie brackets as follows:ei, ej] = 0 for all i = j. Then V is a Lie algebra over F.Let A =  : V → × bys = 0.4 ∈ . By routine computations, it is easy to see that A is not an -bifuzzy Lie subalgebra of L.We define a bifuzzy set A in L, we denote L = {x ∈ L : μ(x) > 0 and ν(x) < 1}.For a bifuzzy set A =  be an -bifuzzy Lie subalgebra of L; then the nonzero set L is a Lie subalgebra of L.Let x, y ∈ L. Then μA(x) > 0 and νA(x) < 1, μA(y) > 0 and νA(y) < 1. Assume that μA(x + y) = 0 and νA(x + y) = 1. If γ ∈ {∈, ∈∨q}, then we can see that x(μA(x), νA(x))γA and y(μA(y), νA(y))γA, but δ ∈ {∈, ∈∨q, ∈∧q}, a contradiction. Also, xqA and yqA, but δ ∈ {∈, ∈∨q, ∈∧q}, a contradiction. Thus μA(x + y) > 0 and νA(x + y) < 1. Thus x + y ∈ L. For other conditions the verification is analogous. Consequently L is a Lie subalgebra of L.Let A =  in L is called an -bifuzzy Lie algebra of L if it satisfies the following conditions: (f)x ∈ A, y ∈ A⇒(x + y), max)∈∨qA,(g)x ∈ A⇒(mx)∈∨qA,(h)x ∈ A, y ∈ A⇒, min)∈∨qAA bifuzzy set x, y ∈ L, m ∈ F, s, s1, s2 ∈ .for all A =  be a bifuzzy set in a Lie algebra L. Then A is an -bifuzzy Lie subalgebra of L if and only ifμA(x + y)⩾min(μA(x), μA(y), 0.5), νA(x + y) ⩽ max(νA(x), νA(y), 0.5),μa(mx)⩾min(μA(x), 0.5), νa(mx) ⩽ max(νA(x), 0.5),μA⩾max(μA(x), μA(y), 0.5), νA ⩽ min(νA(x), νA(y), 0.5)Let x, y ∈ L, m ∈ F.hold for all x, y ∈ L. We consider the following two cases:μA(x), μA(y)) < 0.5, max(νA(x), νA(y)) > 0.5,min)⩾0.5, max) ⩽ 0.5.min((f)⇒(i): Let 1.Case  Assume that μA(x + y) < min(μA(x), μA(y), 0.5), νA(x + y) > max(νA(x), νA(y), 0.5). Then μA(x + y) < min(μA(x), μA(y)), νA(x + y) > max(νA(x), νA(y)). Take s, t such that μA(x + y) < s < min(μA(x), μA(y)), νA(x + y) > t > max(νA(x), νA(y)). Then xs, ys ∈ μA and xt, yt ∈ νA, but f).2.Case  Assume that μA(x + y) < 0.5, νA(x + y) > 0.5. Then x, y ∈ A but x, y ∈ A; then μA(x)⩾s1, μA(y)⩾s2, νA(x) ⩽ t1, νA(y) ⩽ t2. Now, we haves1, s2) > 0.5, max⩾0.5⇒μA(x + y) + min > 1, νA(x + y) ⩽ 0.5⇒νA(x + y) + max < 1. On the other hand, if min ⩽ 0.5, max⩾0.5, then μA(x + y)⩾min, νA(x + y) ⩽ max. Hence (x + y), max)∈∨qA. The verification of (g)⇔(j) and (h)⇔(k) is analogous and we omit the details. This completes the proof.A =  be a bifuzzy set of Lie algebra of L. Then A is an -bifuzzy Li subalgebra of L if and only if each nonempty As,t) is a Lie subalgebra of L.Let A =  is an -bifuzzy Lie subalgebra of L and let s ∈ . If x, y ∈ As,t) ≥ s and μA(y) ≥ s, νA(x) ≤ t and νA(y) ≤ t. Thus,x + y, mx,  ∈ As,t) are Lie subalgebras of L. The proof of converse part is obvious. This ends the proof.Assume that A be a bifuzzy set in a Lie algebra L. Then As,t), 0.5)⩾min(μA(x), μA(y)), min(νA(x + y), 0.5) ⩽ max(νA(x), νA(y)),max(μA(mx), 0.5)⩾μA(x), min(νA(mx), 0.5) ⩽ νA(x),max, 0.5))⩾min(μA(x), μA(y)), min, 0.5)) ⩽ max(νA(x), νA(y)) for all x, y ∈ L, m ∈ F.max, 0.5) < min(μA(x), μA(y)) = s, min(νA(x + y), 0.5) > max(νA(x), νA(y)) = t for some x, y ∈ L; then s ∈ , μA(x + y) < s, νA(x + y) > t, x, y ∈ As,t)( or μA(x + y)⩾s, νA(x + y) ⩽ t, which is contradiction with μA(x + y) < s, νA(x + y) > t. Hence (1) holds. For (2), (3) the verification is analogous.Suppose that s ∈ , x, y ∈ As,t)–(3) hold. Assume that q)-bifuzzy Lie subalgebras of L is an -bifuzzy Lie subalgebra.The intersection of any family of -bifuzzy Lie subalgebra of L and let A : = ⋂i∈ΛAi = . Let x, y ∈ L, then by μA(x + y)⩾min(μA(x), μA(y), 0.5), νA(x + y) ⩽ max(νA(x), νA(y), 0.5), and henceA is an -bifuzzy Lie subalgebra of L.Let {L0 ⊂ L1 ⊂ ⋯⊂Ln = L be a strictly increasing chain of -bifuzzy Lie subalgebras of a Lie algebra L; then there exists -bifuzzy Lie subalgebra A =  of L whose level subalgebras are precisely the members of the chain with A0.5 =  = L.Let r, s ∈  and fuzzy subset μ in L, denotes μ〉r = {x ∈ L | xrqμ}, [μ]r = {x ∈ L | xr ∈ ∨qμ}, r, s ∈ .For any We state here a nice characterization without proof.L be a Lie algebra and A a bifuzzy set in L. Then A is an -bifuzzy Lie subalgebra of L if and only if nonempty subsets L for all r ∈ r and L for all r ∈ -bifuzzy Lie subalgebra of L if and only if nonempty subsets [μA]r and L for all r, s ∈  be a bifuzzy soft set over L. Then  is said to be a bifuzzy soft Lie subalgebra over L if f(x) is a bifuzzy Lie subalgebra of L for all x ∈ A; that is, a bifuzzy soft set  on L is called a bifuzzy soft Lie subalgebra of L if μfɛ(x + y)⩾min{μfɛ(x), μfɛ(y)},νfɛ(x + y) ⩽ max{νfɛ(x), νfɛ(y)},μfɛ(mx)⩾μfɛ(x),νfɛ(mx) ⩽ μfɛ(x),μfɛ⩾min{μfɛ(x), μfɛ(y)},νfɛ ⩽ max{νfɛ(x), νfɛ(y)}Let x, y ∈ L and m ∈ K.hold for all ℜ2 = { : x, y ∈ ℝ} be the set of all 2-dimensional real vectors. Then ℜ2 with  = x × y is a real Lie algebra. Let ℕ and ℤ denote the set of all natural numbers and the set of all integers, respectively. Define f : ℤ → ℜ2 by f(n) = fn : ℜ2 →  ×  for all n ∈ ℤ,f, ℤ) is a bifuzzy soft Lie subalgebra of ℜ2.Let The following proposition is obvious.f, A) be a bifuzzy soft Lie subalgebra of L; then Let  be a bifuzzy soft set over U. For each s, t ∈ , the set s,t) is called an -level soft set of , where fɛs,t)( = {x ∈ U | μfɛ(x) ≥ s, νfɛ(x) ≤ t} for all ɛ ∈ A.Let  be a bifuzzy soft set over L.  is a bifuzzy soft Lie subalgebra if and only if s,t) is a bifuzzy soft Lie subalgebra. For each s, t ∈ , ɛ ∈ A, and x1, x2 ∈ ɛs,t) ≥ s, μfɛ(x2) ≥ s and νfɛ(x1) ≤ t, νfɛ(x2) ≤ t. From f, A)ɛs,t) ≥ min(μfɛ(x1), μfɛ(x2)), μfɛ(x1 + x2) ≥ s, νfɛ(x1 + x2) ≤ max(νfɛ(x1), νfɛ(x2)), νfɛ(x1 + x2) ≤ t. This implies that x1 + x2 ∈ ɛs,t)ɛs,t)s,t)s,t), μfɛ(x2)} and let t = max{νfɛ(x1), νfɛ(x2)}; then x1, x2 ∈ ɛs,t)ɛs,t)ɛs,t)(. This means that μfɛ(x1 + x2) ≥ min(μfɛ(x1), μfɛ(x2)), νfɛ(x1 + x2) ≤ max(νfɛ(x1), νfɛ(x2)). Verification for other conditions is similar. Hence we omit the details. Thus, ɛs,t) is a bifuzzy soft Lie subalgebra over L. This completes the proof.Conversely, assume that  is called a bifuzzy soft function from X to Y.Let f, A) and  be two bifuzzy soft sets over L1 and L2, respectively, and let  be a bifuzzy soft function from L1 to L2.(1)f, A) under the bifuzzy soft function , denoted by , is the bifuzzy soft set on L2 defined by  = (ϕ(f), ψ(A)), where for all k ∈ ψ(A), y ∈ L2The image of ((2)g, B) under the bifuzzy soft function , denoted by −1, is the bifuzzy soft set over L1 defined by −1 = (ϕ−1(g), ψ−1(B)), where for all a ∈ ψ−1(A), for all x ∈ L1,The preimage of  be a bifuzzy soft function from L1 to L2. If ϕ is a homomorphism from L1 to L2, then  is said to be bifuzzy soft homomorphism. If ϕ is a isomorphism from L1 to L2 and ψ is one-to-one mapping from A onto B then  is said to be bifuzzy soft isomorphism.Let  be a bifuzzy soft Lie subalgebra over L2 and let  be a bifuzzy soft homomorphism from L1 to L2. Then −1 is a bifuzzy soft Lie subalgebra over L1.Let −1 is a bifuzzy soft Lie subalgebra over L1.Let f, A) be a bifuzzy soft Lie subalgebra over L1 and let  be a bifuzzy soft homomorphism from L1 to L2. Then  may not be a bifuzzy soft Lie subalgebra over L2.Let  be a bifuzzy soft Lie subalgebra over L and let { | i ∈ I} be a nonempty family of bifuzzy soft Lie subalgebras of . Then f, A);i∈I is a bifuzzy soft Lie subalgebra of ⋀i∈I;⋀Bi∩Bj = ∅ for all i, j ∈ I, then if Let  be an -bifuzzy soft Lie subalgebra over L and let { | i ∈ I} be a nonempty family of -bifuzzy soft K-subalgebras of ; then q)-bifuzzy soft Lie subalgebra of ;i∈I is an -bifuzzy soft Lie subalgebra of ⋀i∈I;⋀Bi∩Bj = ∅ for all i, j ∈ I, then q)- bifuzzy soft Lie subalgebra of if Let  and  be two -bifuzzy soft K-subalgebras over a Lie algebra L. Then q)-bifuzzy soft Lie subalgebra over L.Let . Then h(α) = f(α) is an -bifuzzy Lie subalgebra of L since  is an -bifuzzy soft Lie subalgebra over L.2.Case  Consider (α ∈ B − A). Then h(α) = g(α) is an -bifuzzy Lie subalgebra of L since  is an -bifuzzy soft Lie subalgebra over L.3.Case  Consider (α ∈ A∩B). Then h(α) = f(α)∩g(α) is an -bifuzzy Lie subalgebra of L by the assumption. Thus, in any case, h(α) is an -bifuzzy Lie subalgebra of L. Therefore, q)-bifuzzy soft Lie subalgebra over L.f, A) and  be two -bifuzzy soft K-subalgebras over a Lie algebra L. If A and B are disjoint, then q)-bifuzzy softLie subalgebra over L.Let  and  intuitionistic bifuzzy soft sets on G. If  and  are -intuitionistic bifuzzy soft Lie subalgebra on L, then so are ∩ and f, A) and  are an -bifuzzy soft Lie subalgebra on L and an -bifuzzy soft Lie subalgebra on L, then Let L be a Lie algebra and  and  bifuzzy soft sets on L. If  and  are -bifuzzy soft Lie subalgebra on L, then so are ∪ and Let 𝕊𝕀 the set of all -bifuzzy soft Lie subalgebras on L.Denote by f, A),  ∈ 𝔽𝕊𝕀, by above Lemmas, f, A)∩ ∈ 𝔽𝕊𝕀. It is obvious that f, A)∩ are the least upper bound and the greatest lower bound of  and , respectively. There is no difficulty in replacing {, } with an arbitrary family of 𝔽𝕊𝕀 and so f, A), ,  ∈ 𝔽𝕊𝕀. Suppose thatɛ ∈ A∩(B ∪ C), it follows that ɛ ∈ A and ɛ ∈ B ∪ C. We consider the following cases.For any . Then I(ɛ) = f(ɛ)∩h(ɛ) = J(ɛ).2.Case  Consider . Then I(ɛ) = f(ɛ)∩G(ɛ) = J(ɛ).3.Case  Consider . Then I(ɛ) = f(ɛ)∩(g(ɛ) ∪ h(ɛ)) = (f(ɛ)∩g(ɛ)) ∪ (f(ɛ)∩h(ɛ)) = J(ɛ).I and J are the same operators, and so Therefore, f, A) and  over a Lie algebra is a bifuzzy soft set over G, denoted by , where C = A ∪ B andɛ ∈ C. This is denoted by  = ⊙.The product of two bifuzzy soft sets , , , and  be bifuzzy soft sets over a Lie algebra L such that ⊂ and ⊂. Then f1, A)⊙⊂⊙,∩⊂∩ and ∪⊂∪ and , , and  be bifuzzy soft sets over a Lie algebra L. Then ⊙⊙) = ⊙)⊙.Let ,  ∈ 𝔽𝕊A(G).Now we consider the bifuzzy soft sets over a definite parameter set. Let f, A) and  be -bifuzzy soft Lie subalgebra over a Lie algebra L. Then so is ⊙.Let , ⊙, ∩) is a complete lattice under the relation ⊂.Let Presently, science and technology are featured with complex processes and phenomena for which complete information is not always available. For such cases, mathematical models are developed to handle various types of systems containing elements of uncertainty. A large number of these models are based on an extension of the ordinary set theory such as bifuzzy sets and soft sets. In the current paper, we have presented the basic properties on bifuzzy soft Lie subalgebras. The most of these properties can be simply extended to bifuzzy soft Lie ideals. A Lie algebra is known algebraic structure and there are still many unsolved problems in it. In our opinion the future study of Lie algebras can be extended with the study of (i) roughness in Lie algebras and (ii) fuzzy rough Lie algebras.