Tissue tension and not interphase cell shape determines cell division orientation in the Drosophila follicular epithelium.

We investigated the cell behaviors that drive morphogenesis of the Drosophila follicular epithelium during expansion and elongation of early-stage egg chambers. We found that cell division is not required for elongation of the early follicular epithelium, but drives the tissue toward optimal geometric packing. We examined the orientation of cell divisions with respect to the planar tissue axis and found a bias toward the primary direction of tissue expansion. However, interphase cell shapes demonstrate the opposite bias. Hertwig's rule, which holds that cell elongation determines division orientation, is therefore broken in this tissue. This observation cannot be explained by the anisotropic activity of the conserved Pins/Mud spindle-orienting machinery, which controls division orientation in the apical-basal axis and planar division orientation in other epithelial tissues. Rather, cortical tension at the apical surface translates into planar division orientation in a manner dependent on Canoe/Afadin, which links actomyosin to adherens junctions. These findings demonstrate that division orientation in different axes-apical-basal and planar-is controlled by distinct, independent mechanisms in a proliferating epithelium.

Brain size predicts behavioural plasticity in guppies (Poecilia reticulata): An experiment.

Understanding how animal personality (consistent between-individual behavioural differences) arises has become a central topic in behavioural sciences. This endeavour is complicated by the fact that not only the mean behaviour of individuals (behavioural type) but also the strength of their reaction to environmental change (behavioural plasticity) varies consistently. Personality and cognitive abilities are linked, and we suggest that behavioural plasticity could also be explained by differences in brain size (a proxy for cognitive abilities), since accurate decisions are likely essential to make behavioural plasticity beneficial. We test this idea in guppies (Poecilia reticulata), artificially selected for large and small brain size, which show clear cognitive differences between selection lines. To test whether those lines differed in behavioural plasticity, we reared them in groups in structurally enriched environments and then placed adults individually into empty tanks, where we presented them daily with visual predator cues and monitored their behaviour for 20 days with video-aided motion tracking. We found that individuals differed consistently in activity and risk-taking, as well as in behavioural plasticity. In activity, only the large-brained lines demonstrated habituation (increased activity) to the new environment, whereas in risk-taking, we found sensitization (decreased risk-taking) in both brain size lines. We conclude that brain size, potentially via increasing cognitive abilities, may increase behavioural plasticity, which in turn can improve habituation to novel environments. However, the effects seem to be behaviour-specific. Our results suggest that brain size likely explains some of the variation in behavioural plasticity found at the intraspecific level.

The effect of an e-learning module on health sciences students' venipuncture skill development.

INTRODUCTION: Venipuncture is a psychomotor skill required in many healthcare professions. E-learning could be used to overcome current barriers in face-to-face learning in healthcare education such as insufficient classroom space or qualified instructors. We sought to evaluate the effectiveness of an e-learning module on students' performance when used in addition to in-class training. METHODS: Overall, 224 health sciences students were approached to participate in this pilot study. Recruited students were divided into control and study groups. The control group received only in-class training, whereas the study group had access to the e-learning module in addition to in-class learning. Both groups were evaluated on their self-confidence using a Likert scale, academic competence using a multiple-choice questionnaire, and psychomotor competence from video skill recordings using an in-house rubric. Nonparametric, independent sample Mann-Whitney tests were performed to evaluate differences between groups. RESULTS: Overall, 114 students provided written informed consent; 84 students (control: n = 50, study: n = 34) participated in at least one component of the study. Significantly higher (p = 0.017) academic competence scores were observed in the study group. Significantly higher confidence levels were also observed postintervention for both the control (p = 0.0025) and study (p = 0.0011) groups; however, no significant differences were found between the study and control groups before (p = 0.441) or after (p = 0.883) intervention. Finally, no significant differences (p = 0.428) were observed for psychomotor skills between the study arms. CONCLUSION: Our results suggest that there is potential for e-learning to increase the academic competence of students when used in conjunction with traditional learning; however, further research is needed to determine its efficacy on psychomotor skills.

Context- and Output Layer-Dependent Long-Term Ensemble Plasticity in a Sensory Circuit.

Sensory information is translated into ensemble representations by various populations of projection neurons in brain circuits. The dynamics of ensemble representations formed by distinct channels of output neurons in diverse behavioral contexts remains largely unknown. We studied the two output neuron layers in the olfactory bulb (OB), mitral and tufted cells, using chronic two-photon calcium imaging in awake mice. Both output populations displayed similar odor response profiles. During passive sensory experience, both populations showed reorganization of ensemble odor representations yet stable pattern separation across days. Intriguingly, during active odor discrimination learning, mitral but not tufted cells exhibited improved pattern separation, although both populations showed reorganization of ensemble representations. An olfactory circuitry model suggests that cortical feedback on OB interneurons can trigger both forms of plasticity. In conclusion, we show that different OB output layers display unique context-dependent long-term ensemble plasticity, allowing parallel transfer of non-redundant sensory information to downstream centers. VIDEO ABSTRACT.

LINX®, a novel treatment for patients with refractory asthma complicated by gastroesophageal reflux disease: a case report.

BACKGROUND: Gastroesophageal reflux disease is one of the most common comorbidities in patients with asthma. Gastroesophageal reflux disease can be linked to difficult-to-control asthma. Current management includes gastric acid suppression therapy and surgical antireflux procedures. The LINX® procedure is a novel surgical treatment for patients with gastroesophageal reflux disease refractory to medical therapy. To the best of our knowledge, we report the first case of successful treatment of refractory asthma secondary to gastroesophageal reflux disease using the LINX® procedure. CASE PRESENTATION: Our patient was a 22-year-old white woman who met the American Thoracic Society criteria for refractory asthma that had remained poorly controlled for 5 years despite progressive escalation to step 6 treatment as recommended by National Institutes of Health-National Asthma Education and Prevention Program guidelines, including high-dose oral corticosteroids, high-dose inhaled corticosteroid plus long-acting ß2-agonist, leukotriene receptor antagonist, and monthly omalizumab. Separate trials with azithromycin therapy and roflumilast did not improve her asthma control, nor did bronchial thermoplasty help. Additional consultations with two other university health systems left the patient with few treatment options for asthma, which included cyclophosphamide. Instead, the patient underwent a LINX® procedure after failure of maximal medical therapy for gastroesophageal reflux disease with the additional aim of improving asthma control. After she underwent LINX® treatment, her asthma improved dramatically and was no longer refractory. She had normal exhaled nitric oxide levels and loss of peripheral eosinophilia after LINX® treatment. Prednisone was discontinued without loss of asthma control. The only immediate adverse effects due to the LINX® procedure were bloating, nausea, and vomiting. CONCLUSIONS: LINX® is a viable alternative to the Nissen fundoplication procedure for the treatment of patients with gastroesophageal reflux disease and poorly controlled concomitant refractory asthma.

Evaluation of ambiguous associations in the amygdala by learning the structure of the environment.

Recognizing predictive relationships is critical for survival, but an understanding of the underlying neural mechanisms remains elusive. In particular, it is unclear how the brain distinguishes predictive relationships from spurious ones when evidence about a relationship is ambiguous, or how it computes predictions given such uncertainty. To better understand this process, we introduced ambiguity into an associative learning task by presenting aversive outcomes both in the presence and in the absence of a predictive cue. Electrophysiological and optogenetic approaches revealed that amygdala neurons directly regulated and tracked the effects of ambiguity on learning. Contrary to established accounts of associative learning, however, interference from competing associations was not required to assess an ambiguous cue-outcome contingency. Instead, animals' behavior was explained by a normative account that evaluates different models of the environment's statistical structure. These findings suggest an alternative view of amygdala circuits in resolving ambiguity during aversive learning.

Pulmonary Artery Abnormalities in Ex-smokers with and without Airflow Obstruction.

Pulmonary vascular disease is a common complication of chronic obstructive pulmonary disease (COPD), and an important risk factor for COPD exacerbations and death. We explored the relationship between pulmonary artery volumes measured using thoracic computed tomography (CT) and lung structure-function measured using spirometry, CT and magnetic resonance imaging (MRI) in 124 ex-smokers with (n = 68) and without (n = 56) airflow obstruction, and a control group of 35 never-smokers. We observed significantly greater main (p = .01), right (p = .001) and total (p = .003) pulmonary artery volumes in ex-smokers with airflow obstruction as compared to ex-smokers without airflow obstruction. There were also significantly greater pulmonary artery volumes in both ex-smoker subgroups, compared to the never-smoker subgroup (p = .008). For all participants, there were significant correlations for pulmonary artery volumes with the ratio of the forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC), the diffusing capacity of the lung for carbon monoxide (DLCO%pred), airway count, MRI ventilation defect percent and MRI apparent diffusion coefficients. In ex-smokers, ventilation defect percent was significantly correlated with right (r = 0.27, p = .02) and total (r = 0.25, p = .03) pulmonary artery volumes. Multivariate zero-inflated Poisson regression analysis showed that FEV1%pred (p = .004), DLCO%pred (p = .03), the six minute walk distance (p = .04) and total pulmonary artery volume (p = .03) were significant predictors of acute exacerbations of COPD, while the number of previous exacerbations was not. In conclusion, pulmonary artery enlargement measured using thoracic CT was observed even in ex-smokers without airflow obstruction and was predictive of COPD exacerbations in ex-smokers with airflow obstruction.

Pulmonary abnormalities and carotid atherosclerosis in ex-smokers without airflow limitation.

It is well-established that COPD patients have a burden of vascular disease that cannot be fully-explained by smoking history but the mechanistic links between atherosclerosis and pulmonary disease in COPD patients are not well-understood. Moreover, in ex-smokers without symptoms or other evidence of COPD, subclinical pulmonary and vascular disease, although potentially present, has not been described or evaluated. Hence our aim was to use sensitive three-dimensional (3D) pulmonary and carotid imaging to quantify pulmonary airway/parenchyma abnormalities and atherosclerosis in ex-smokers without airflow limitation or symptoms consistent with COPD. We evaluated 61 subjects without airflow limitation including 34 never- (72 ± 6 years) and 27 ex-smokers (73 ± 9 years), who provided written informed consent to spirometry, plethysmography, (3)He magnetic resonance imaging (MRI) and carotid ultrasound (US) and, for ex-smokers alone, thoracic X-ray computed tomography (CT). Ex-smokers had significantly greater (3)He ventilation defect percent (VDP = 7%, p = 0.001) and carotid total plaque volume (TPV = 250 mm(3), p = 0.002) than never-smokers, although there were no significant differences for spirometry or plethysmography, and CT airway and emphysema measurements were normal. There were univariate relationships for (3)He VDP with carotid intima media thickness (IMT, r = 0.42, p = 0.004), TPV (r = 0.41, p = 0.006) and vessel wall volume (VWV, r = 0.40, p = 0.007). Multivariate models that included age, BMI, FEV1, DLCO and VDP showed that only VDP significantly predicted IMT (ß = 0.41, p = 0.001), VWV (ß = 0.45, p = 0.003) and TPV (ß = 0.38, p = 0.005). In summary, there was imaging evidence of mild airways disease and carotid plaque burden that were related and significantly greater in ex-smokers without airflow limitation than in never-smokers.

No personality without experience? A test on Rana dalmatina tadpoles.

While the number of studies reporting the presence of individual behavioral consistency (animal personality, behavioral syndrome) has boomed in the recent years, there is still much controversy about the proximate and ultimate mechanisms resulting in the phenomenon. For instance, direct environmental effects during ontogeny (phenotypic plasticity) as the proximate mechanism behind the emergence of consistent individual differences in behavior are usually overlooked compared to environmental effects operating across generations (genetic adaptation). Here, we tested the effects of sociality and perceived predation risk during ontogeny on the strength of behavioral consistency in agile frog (Rana dalmatina) tadpoles in a factorial common garden experiment. Tadpoles reared alone and without predatory cues showed zero repeatability within (i.e., lack of personality) and zero correlation between (i.e., lack of syndrome) activity and risk-taking. On the other hand, cues from predators alone induced both activity and risk-taking personalities, while cues from predators and conspecifics together resulted in an activity - risk-taking behavioral syndrome. Our results show that individual experience has an unequivocal role in the emergence of behavioral consistency. In this particular case, the development of behavioral consistency was most likely the result of genotype × environment interactions, or with other words, individual variation in behavioral plasticity.

Robotic cholecystectomy and resident education: the UC Davis experience.

INTRODUCTION: The popularity of robotic surgery highlights the need for strategies to integrate this technique into surgical education. We present 5 year data for robotic cholecystectomy (RC) as a model for training residents. METHODS: Data were collected on all RC over 66 months. Duration for docking the robot (S2) and performing RC (S3), and surgical outcomes, were recorded. We used a linear mixed effects model to investigate learning curves. RESULTS: Thirty-eight trainees performed 160 RCs, with most performing more than four. One case was aborted due to haemodynamic instability, and two were converted to open surgery due to adhesions. There were no technical complications. The duration of S2 (mean = 6.2 ± 3.6 min) decreased considerably (p = 0.027). Trainees also demonstrated decrease in duration of S3 (mean = 38.4 ± 15.4 min), indicating improvement in technique (p = 0.008). CONCLUSIONS: RC is an effective model for teaching residents. Significant and reproducible improvement can be realized with low risk of adverse outcomes.

Single-site robotic cholecystectomy in a broadly inclusive patient population: a prospective study.

OBJECTIVES: To describe our initial experience with single-site robotic cholecystectomy (SSRC) and its applicability to a broad segment of patients. BACKGROUND: At the initiation of our study, there were only 3 published reports on SSRC. These initial studies had limited inclusion criteria. We present our experience with the technical aspects and patient outcomes of SSRC in a broadly inclusive patient population. METHODS: Prospective cohort study from January 2012 to January 2013, in which 95 patients underwent SSRC. Procedural times, postoperative complications, delayed hospital discharges, and re-admissions were evaluated. RESULTS: Patients were predominantly female (71.6%) had mean age of 45.2 ± 6.1 years and mean body mass index (BMI) of 30.1 ± 7.1 kg/m. Overall, mean total operative time (TOT) for all patients (n = 95) was 88.63 ± 32.0 (range: 49-220) minutes. SSRC was not completed in 8 (8.42%) patients: 6 conversions to laparoscopy, 1 conversion to open, and 1 aborted case. The group of patients who were able to complete SSRC (n = 87) had a mean TOT of 83.5 ± 24.5 minutes and mean operative robotic time (RT) of 39.6 ± 15.2 minutes. RT was longer in patients with intra-abdominal adhesions (P = 0.0139) and higher BMI (P = 0.03). A minority of patients required hospital admission (11.6%), readmission (6.3%), or reoperation (1.1%). No bile duct injury or death occurred. CONCLUSIONS: SSRC is safe and has a manageable learning curve. Patient factors, such as obesity, did not significantly affect conversion rates or TOTs. SSRC is a promising new technique, which can be offered to a wide array of patients.

One, two and three-dimensional ultrasound measurements of carotid atherosclerosis before and after cardiac rehabilitation: preliminary results of a randomized controlled trial.

BACKGROUND: It is still not known how patients who are post-transient ischemic attack (TIA) or post-stroke might benefit from prospectively planned comprehensive cardiac rehabilitation (CCR). In this pilot evaluation of a larger ongoing randomized-controlled-trial, we evaluated ultrasound (US) measurements of carotid atherosclerosis in subjects following TIA or mild non-disabling stroke and their relationship with risk factors before and after 6-months of CCR. METHODS: Carotid ultrasound (US) measurements of one-dimensional intima-media-thickness (IMT), two-dimensional total-plaque-area (TPA), three-dimensional total-plaque-volume (TPV) and vessel-wall-volume (VWV) were acquired before and after 6-months CCR for 39 subjects who had previously experienced a TIA and provided written informed consent to participate in this randomized controlled trial. We maintained blinding for this ongoing study by representing treatment and control groups as A or B, although we did not identify which of A or B was treatment or control. Carotid IMT, TPA, TPV and VWV were measured before and after CCR as were changes in body mass index (BMI), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), systolic blood pressure (SBP) and diastolic blood pressure (DBP). RESULTS: There were no significant differences in US measurements or risk factors between groups A and B. There was no significant change in carotid ultrasound measurements for group A (IMT, p = .728; TPA, p = .629; TPV, p = .674; VWV, p = .507) or B (IMT, p = .054; TPA, p = .567; TPV, p = .773; VWV, p = .431) at the end of CCR. There were significant but weak-to-moderate correlations between IMT and VWV (r = 0.25, p = .01), IMT and TPV (r = 0.21, p = .01), TPV and TPA (r = 0.60, p < .0001) and VWV and TPV (r = 0.22, p = .02). Subjects with improved TC/HDL ratios showed improved carotid VWV although, this was not statistically significant. CONCLUSION: In this preliminary evaluation, there were no significant differences in carotid US measurements in the control or CCR group; a larger sample size and/or longer duration is required to detect significant changes in US or other risk factor measurements.

Comparison of robotic and laparoendoscopic single-site surgery systems in a suturing and knot tying task.

BACKGROUND: Laparoendoscopic single-site (LESS) surgery has been established for various procedures. Shortcomings of LESS surgery include loss of triangulation, instrument collisions, and poor ergonomics, making advanced laparoscopic tasks especially challenging. We compared a LESS system with a robotic single-site surgery platform in performance of a suturing and knot-tying task under clinically simulated conditions. METHODS: Each of five volunteer minimally invasive surgeons was tasked with suturing a 5 cm longitudinal enterotomy in porcine small intestine with square knots at either end, using a laparoendoscopic or da Vinci robotic single-site surgery platform, within a 20 min time limit. A saline leak test was then performed. Each surgeon performed the task twice using each system. The time to completion of the task and presence of a leak were noted. Fisher's exact test was used to compare the overall completion rate within the defined time limit, and a Wilcoxon rank test was used to compare the specific times to complete the task. A p value of <0.05 was considered significant. RESULTS: All surgeons were able to complete the task on the first try within 20 min using the robot system; 60% of surgeons were able to complete it after two attempts using the LESS surgery system. Time to completion using the robot system was significantly shorter than the time using the standard LESS system (p < 0.0001). There were no leaks after closure with the robot system; the leak rate following the standard LESS system was 90%. CONCLUSIONS: Surgeons demonstrated significantly better suturing and knot-tying capabilities using the robot single-site system compared to a standard LESS system. The robotic system has the potential to expand single-site surgery to more complex tasks.

Increased soluble leptin receptor levels in morbidly obese patients with insulin resistance and nonalcoholic fatty liver disease.

The adipocyte hormone, leptin has been demonstrated to have profibrogenic actions in vitro and in animal models. However, no correlation was found between plasma leptin levels and fibrosis stage in humans. Thus, our aim was to study whether soluble leptin receptor (SLR) or free leptin index (FLI; calculated as the ratio of leptin to SLR), may correlate better with the features of metabolic syndrome and with the histological grade and stage of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). We studied a population (n = 104) of morbidly obese patients undergoing bariatric surgery. Data including BMI, type 2 diabetes mellitus, hypertension, and hyperlipidemia were obtained. Plasma fasting leptin and SLR, fasting glucose and insulin were measured, and homeostasis model of assessment insulin resistance (HOMA(IR)) index and FLI were calculated. All patients had intraoperative liver biopsies. Leptin levels correlated with the BMI. The multiple regression analysis indicated that increasing HOMA and decreasing FLI were predictors of steatosis in the liver (P < 0.0003). SLR levels were positively correlated with the presence of diabetes mellitus and the stage of fibrosis. In conclusion, increased SLR levels in morbidly obese patients with diabetes are correlated with the stage of liver fibrosis, and may reflect progressive liver disease.

3-D telestration: a teaching tool for robotic surgery.

BACKGROUND: Telestration is an important teaching tool in minimally invasive surgery (MIS). While robotic surgery offers the added benefit of three-dimensional (3-D) visualization, telestration technology does not currently exist for this modality. This project aimed to develop a video algorithm to accurately translate a mentor's two-dimensional (2-D) telestration into a 3-D telestration in the da Vinci visual field. MATERIALS AND METHODS: A prototype 3-D telestration system was constructed to translate 2-D telestration from a mentor station into 3-D graphics for the trainee at the robotic console. This system uses fast image correlation algorithms to allow 2-D images to be placed over the same anatomic location in the two separate video channels of the stereoscopic robotic visualization system. Three subjects of varying surgical backgrounds, blinded to the mode of telestration (2-D vs. 3-D), were tested in the laboratory, using a simulated robotic task. RESULTS: There were few technologic errors (2), only one of which resulted in a task error, in 99 total trials. Only the experienced MIS staff surgeon had a significantly faster task time in 2-D than in 3-D (P < 0.05). The MIS fellow recorded the fastest task times in 2-D and 3-D (P < 0.05). There were nine task errors, six of which were committed by the MIS fellow. The nonsurgeon trainee had the least number of errors but also had the slowest times. CONCLUSIONS: Robotic telestration in 3-D is feasible and does not negatively impact performance in laboratory tasks. We plan to refine the prototype and investigate its use in vivo.

Robotic cholecystectomy: learning curve, advantages, and limitations.

BACKGROUND: Robotic cholecystectomy is safe, feasible procedure. Initial studies showed significant set up time and operating time but no clear clinical advantage of the robotic involvement. We have investigated the learning curve, advantages and limitation of the procedure. MATERIAL AND METHODS: We reviewed all (n = 51) robotic cholecystectomies performed between July 2004 and December 2005. The surgery was performed using the da Vinci system. We recorded operative time, setup time of robotics instrumentation, conversion to laparoscopic or open cholecystectomy and complication of the procedure. RESULTS: Forty-eight of the 51 procedures (94%) were completed robotically. We did not experience any significant complications directly related to robotics surgery. The mean +/- SD operating time was 77 +/- 22.3 min. The mean setup time for robotics (from incision until robot was in place, including draping the robot) was 24 +/- 8.8 min. However, the setup time significantly improved as we gained more experience: from 30.6 +/- 10.7 min (first 16 cases) to 18.3 +/- 4.0 min (cases 33-48). The mean robotic time was 34 +/- 16.1 min. We observed no significant improvement in robotic procedure time. CONCLUSIONS: Robotic cholecystectomy offers significant advantages such as three-dimensional view, easier instrument manipulations and possibility of remote site surgery. We observed some shortcomings of robotic surgery such as need for larger and additional ports, and need for undocking the machine in case of cholangiography or change of patient position. Our data shows that the learning curve is between 16 to 32 procedures to significantly decrease the setup time and total operating time.

Differential expression of potassium currents in Deiters cells of the guinea pig cochlea.

Among the supporting cells, Deiters cells are in intimate contact with outer hair cells (OHCs) in the inner ear. The aim of this study was to characterize the outward rectifying K+ current of Deiters cells in conjunction with cellular morphological characteristics. In the majority of cells, the K+ current had a biphasic inactivation kinetics (tau1 and tau2 were 2,735+/-90 (n=77) and 160+/-14 ms (n=72), respectively). The rapidly inactivating current component was more sensitive to Charybdotoxin (ChTx, 10 nM) block whereas the slowly inactivating current could be blocked more efficiently by tetraethylammonium (1 mM). All these point toward the existence of two distinct potassium channel types in these cells. Deiters cells attached to shorter OHCs had more voluminous, whereas those attached to longer OHCs had lanky cell bodies. The inactivation kinetics was slower in cells having corpulent cell bodies due to the increased proportion of the slowly inactivating current component (0.736+/-0.033, n=27) as compared to the one determined for lanky cells (0.522+/-0.023, n=36). The average peak K+ current was higher in Deiters cells connected to OHCs (5,417+/-541 pA, n=40) than in isolated ones (3,527+/-410, n=37). Deiters cells having different cell shapes and showing different K+ channel expression may contribute to the active mechanism of the cochlea to various degrees.

Energy transfer at a gas-liquid interface: kinematics in a prototypical system.

A detailed characterization of collisional energy transfer at a liquid surface not only provides a framework for the interpretation of experimental studies but also affords insight into energy feedback mechanisms that may be important in multiphase combustion processes. We address this problem by performing simulations of a prototypical Lennard-Jones system, investigating the dependence of the energy transfer and incident-atom trapping probability on the liquid temperature, on the mass and angle of incidence of the impinging atom, and on the strength of the gas-liquid interaction. In general, in agreement with the results of experiments, these calculations point to the dominance of kinematic effects in determining the gross energy transfer, but they also attest to the important role played by surface roughening in the enhancement of energy transfer that accompanies an increase in the liquid temperature.

Changes in purinoceptor distribution and intracellular calcium levels following noise exposure in the outer hair cells of the guinea pig.

Among the cells of the inner ear, the outer hair cells (OHCs) are the most important targets of noise-induced effects, being the most sensitive cell types. The aim of this study was to examine the effects of noise (50 Hz-20 kHz, 80 dB sound pressure level, 14 days) on intracellular calcium levels and on the expression pattern of purinoceptors in the membrane of the OHCs of the guinea pig and to measure the stiffness changes of the lateral membrane of these cells. In noise-exposed animals, the resting intracellular calcium concentration increased compared to nontreated animals and was slightly higher in the cells of the basal (219 +/- 29 nM: ) than in the apical (181 +/- 24 nM: ) turns of the cochlea. After application of 180 muM: adenosine triphosphate, the intracellular calcium level rose by 60 +/- 22 nM: in cells from the apical and by 44 +/- 10 nM: in cells from the basal turns, significantly less than in nontreated animals. Expression of the P(2X1), P(2X2), P(2X4), P(2X7), P(2Y1) and P(2Y4) receptor subtypes was suppressed, while expression of the P(2Y2) subtype did not decrease in either of the two preparations. In parallel with the increase in intracellular calcium concentration, the stiffness of the lateral wall of the OHCs was increased. Noise-induced changes in intracellular calcium homeostasis and subsequently in the calcium-dependent regulatory mechanisms may modify OHC lateral wall stiffness and may lead to reduction of the efficacy of the cochlear amplifier.