Nonlinear decision-making with enzymatic neural networks.

Artificial neural networks have revolutionized electronic computing. Similarly, molecular networks with neuromorphic architectures may enable molecular decision-making on a level comparable to gene regulatory networks1,2. Non-enzymatic networks could in principle support neuromorphic architectures, and seminal proofs-of-principle have been reported3,4. However, leakages (that is, the unwanted release of species), as well as issues with sensitivity, speed, preparation and the lack of strong nonlinear responses, make the composition of layers delicate, and molecular classifications equivalent to a multilayer neural network remain elusive (for example, the partitioning of a concentration space into regions that cannot be linearly separated). Here we introduce DNA-encoded enzymatic neurons with tuneable weights and biases, and which are assembled in multilayer architectures to classify nonlinearly separable regions. We first leverage the sharp decision margin of a neuron to compute various majority functions on 10 bits. We then compose neurons into a two-layer network and synthetize a parametric family of rectangular functions on a microRNA input. Finally, we connect neural and logical computations into a hybrid circuit that recursively partitions a concentration plane according to a decision tree in cell-sized droplets. This computational power and extreme miniaturization open avenues to query and manage molecular systems with complex contents, such as liquid biopsies or DNA databases.

Impact of cirrhosis in patients undergoing laparoscopic liver resection in a nationwide multicentre survey.

BACKGROUND: The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study. METHODS: This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection. RESULTS: Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010). CONCLUSION: Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.

ANTECEDENTES: El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección. RESULTADOS: Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

Advancement of magma fragmentation by inhomogeneous bubble distribution.

Decompression times reported in previous studies suggest that thoroughly brittle fragmentation is unlikely in actual explosive volcanic eruptions. What occurs in practice is brittle-like fragmentation, which is defined as the solid-like fracture of a material whose bulk rheological properties are close to those of a fluid. Through laboratory experiments and numerical simulation, the link between the inhomogeneous structure of bubbles and the development of cracks that may lead to brittle-like fragmentation was clearly demonstrated here. A rapid decompression test was conducted to simulate the fragmentation of a specimen whose pore morphology was revealed by X-ray microtomography. The dynamic response during decompression was observed by high-speed photography. Large variation was observed in the responses of the specimens even among specimens with equal bulk rheological properties. The stress fields of the specimens under decompression computed by finite element analysis shows that the presence of satellite bubbles beneath a large bubble induced the stress concentration. On the basis of the obtained results, a new mechanism for brittle-like fragmentation is proposed. In the proposed scenario, the second nucleation of bubbles near the fragmentation surface is an essential process for the advancement of fragmentation in an upward magma flow in a volcanic conduit.

Case Report of Extensive Isolated Spontaneous Celiac Trunk Dissection After Liver Transplantation.

Arterial dissection is a rare complication after liver transplantation (LT). We report a case of extensive isolated spontaneous celiac trunk dissection (ISCTD) up to the proper hepatic artery, left gastric artery, and splenic artery after living donor liver transplantation. A 48-year-old woman with cryptogenic liver cirrhosis underwent living donor liver transplantation. Intraoperative and postoperative Doppler ultrasound revealed sufficient flow in the hepatic artery, portal vein, and hepatic vein. On postoperative day (POD) 10, Doppler ultrasound showed reduction of hepatic arterial flow. On POD 16, a contrast-enhanced computed tomography scan showed that the ISCTD extended to the proper hepatic artery, left gastric artery, and splenic artery with an entry tear on the proximal side of the celiac trunk. Although the computed tomography scan showed ischemia of a small part of the liver, blood flow to the liver was kept to some extent. Because all false lumens were occluded by thrombi and the liver enzyme levels normalized, we chose conservative therapy with antiplatelet agents. The patient was discharged on POD 53. She remains well without any liver dysfunction after 18 months with reduction in all false lumens and a patent hepatic artery. Several cases of ISCTD have been reported apart from LT, most of which were treated with conservative therapy. We conclude that conservative therapy could be the first choice in ISCTD even after LT.

Effects of the masticatory demand on the rat mandibular development.

The influence of masticatory loading stimulus on mandibular development is not fully clear. In this paper, experimental alterations in the daily muscle use, caused by a changed diet consistency, were continuously monitored, while adaptations in bone and cartilage were examined. It is hypothesised that decreased muscular loading will result in a decrease in the growth factor expression and mandible growth. Fourteen 21-day-old Wistar strain male rats were randomly divided into two groups and fed on either a hard or soft diet for 14 weeks. An implanted radio-telemetric device recorded continuously muscle activity of the superficial masseter muscle. Chondroblast proliferation in the condylar cartilage was identified by insulin-like growth factor-1 receptor (IGF-1r) immunostaining. Furthermore, an X-ray was taken for cephalometric analysis. In the soft-diet group, the duty time of the superficial masseter muscle at higher activity levels was significantly lower than that in the hard-diet group. This decrease in muscular loading of the jaw system was accompanied by: a significant reduction in (i) articular cartilage thickness, (ii) expression of IGF-1r immunopositive cells and (iii) mandible ramus height. In conclusion, a decrease in masticatory demand during the growth period leads to insufficient mandibular development.

A transverse emittance and acceptance measurement system in a low-energy beam transport line.

A transverse beam emittance and acceptance measurement system has been developed to visualize the relationship between the injected beam emittance and the acceptance of a cyclotron. The system is composed of a steering magnet, two pairs of slits to limit the horizontal and vertical phase-space, a beam intensity detector just behind the slits for the emittance measurement, and a beam intensity detector in the cyclotron for the acceptance measurement. The emittance is obtained by scanning the slits and measuring the beam intensity distribution. The acceptance is obtained by measuring the distribution of relative beam transmission by injecting small emittance beams at various positions in a transverse phase-space using the slits. In the acceptance measurement, the beam from an ion source is deflected to the defined region by the slits using the steering magnet so that measurable acceptance area covers a region outside the injection beam emittance. Measurement tests were carried out under the condition of accelerating a beam of (16)O(6+) from 50.2 keV to 160 MeV. The emittance of the injected beam and the acceptance for accelerating and transporting the beam to the entrance of the extraction deflector were successfully measured. The relationship between the emittance and acceptance is visualized by displaying the results in the same phase-plane.

Solid tumor size on high-resolution computed tomography and maximum standardized uptake on positron emission tomography for new clinical T descriptors with T1 lung adenocarcinoma.

BACKGROUND: To better describe clinical T descriptors using solid tumor size (the maximum dimension of the solid component of the tumor) on high-resolution computed tomography (HRCT) and maximum standardized uptake value (SUVmax) on F-18-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT). PATIENTS AND METHODS: We examined 610 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection. Recurrence-free survival (RFS) was assessed on the basis of whole tumor size (maximum dimension of the tumor), solid tumor size, or a combination of solid tumor size and SUVmax. RESULTS: RFS based on whole tumor size was not significantly different between patients with tumors measuring ≤2 cm and 2-3 cm (P = 0.089), whereas RFS based on solid tumor size was significantly different (P < 0.0001). We divided patients into four groups on the basis of solid tumor size and SUVmax: group 1: solid tumor size ≤2 cm, SUVmax ≤1.8; group 2: solid tumor size ≤2 cm, SUVmax >1.8; group 3: solid tumor size 2-3 cm, SUVmax ≤3.6; and group 4: solid tumor size 2-3 cm, SUVmax >3.6. Groups 2 and 3 were combined because they showed similar RFS each other. RFS was significantly different among these groups: group 1 versus groups 2 + 3, P < 0.0001; groups 2 + 3 versus group 4, P = 0.019. CONCLUSIONS: Both solid tumor size on HRCT and SUVmax on FDG-PET/CT reflect prognosis well in patients with clinical stage IA lung adenocarcinoma and may support new clinical T descriptors.

A cross-sectional study of sarcopenia in Japanese men and women: reference values and association with cardiovascular risk factors.

In this study of Japanese men and women, we determine reference values for sarcopenia and test the hypothesis that sarcopenia is associated with risk factors for cardiovascular disease, independent of waist circumference. A total of 1,488 Japanese men and women aged 18-85 years participated in this study. Appendicular muscle mass (AMM) was measured by dual-energy X-ray absorptiometry. Reference values for classes 1 and 2 sarcopenia (skeletal muscle index: AMM/height2, kg m-2) in each sex were defined as values one and two standard deviations below the sex-specific means of reference values obtained in this study from young adults aged 18-40 years. The reference values for class 1 and class 2 sarcopenia were 7.77 and 6.87 kg m-2 in men and 6.12 and 5.46 kg m-2 in women. In subjects both with class 1 and class 2 sarcopenia, body mass index and % body fat were significantly lower than in normal subjects. Despite whole-blood glycohaemoglobin A1c in men with class 1 sarcopenia was significantly higher than in normal subjects, and brachial-ankle pulse wave velocity in women both with class 1 and class 2 sarcopenia were significantly higher than in normal subjects, using one-way ANCOVA with adjustment for the covariate of waist circumference. Although sarcopenia is associated with thin body mass, it is associated with more glycation of serum proteins in men and with greater arterial stiffness in women, independent of waist circumference.

FcepsilonRI-mediated thymic stromal lymphopoietin production by interleukin-4-primed human mast cells.

A significant increase of mRNA expression of thymic stromal lymphopoietin (TSLP) has been reported in the bronchial mast cells (MCs) of asthmatic subjects; however, the mechanism underlying the upregulation of TSLP mRNA and protein remains unknown. FcepsilonRI-mediated activation of human MCs upregulated TSLP mRNA expression by 5.2+/-2.9-fold, while activation of the MCs using lipopolysaccharide and polyriboinosinic:polyribocytidylic acid failed to upregulate TSLP. Stimulation of MCs with interleukin (IL)-4 alone did not affect the TSLP mRNA expression, while pre-incubation of MCs with IL-4 for 48 h significantly enhanced the FcepsilonRI-mediated TSLP mRNA expression (by 53.7+/-15.9-fold; p<0.05) and the amount of TSLP in the cell pellets increased significantly from 23.4+/-4.3 pg mL(-1) to 121.5+/-3.7 pg mL(-1) (p<0.0001). However, the released TSLP was rapidly degraded by proteases that were released by MCs. We identified the population of cells expressing TSLP in the lungs of 16 asthmatic and 11 control subjects by immunohistochemistry. The percentage of TSLP-positive MCs in the total population of MCs was significantly increased in asthmatic airways (p<0.0001). Thus, MCs are able to store TSLP intracellularly and to produce TSLP following aggregation of FcepsilonRI in the presence of IL-4.

Isotopic dependence of the giant monopole resonance in the even-A 112-124Sn isotopes and the asymmetry term in nuclear incompressibility.

The strength distributions of the giant monopole resonance (GMR) have been measured in the even-A Sn isotopes (A=112-124) with inelastic scattering of 400-MeV alpha particles in the angular range 0 degrees -8.5 degrees . We find that the experimentally observed GMR energies of the Sn isotopes are lower than the values predicted by theoretical calculations that reproduce the GMR energies in 208Pb and 90Zr very well. From the GMR data, a value of Ktau = -550 +/- 100 MeV is obtained for the asymmetry term in the nuclear incompressibility.

Complete removal of a bronchial granular cell tumor by bronchoplasty.

A rare case of bronchial granular cell tumor (GCT) arising in the right upper bronchus is presented here, which was completely resected by sleeve lobectomy. The 46-year-old female patient had a three-month history of severe dry coughing, and multimodality imaging revealed a 20 mm-sized GCT of the right upper bronchial orifice. Since endoscopic treatment appeared to be impossible, she underwent right upper sleeve lobectomy and the lesion could be completely removed.

Extraction of weak transition strengths via the (3He, t) reaction at 420 MeV.

Differential cross sections for transitions of known weak strength were measured with the (3He, t) reaction at 420 MeV on targets of 12C, 13C, 18O, 26Mg, 58Ni, 60Ni, 90Zr, 118Sn, 120Sn, and 208Pb. Using these data, it is shown that the proportionalities between strengths and cross sections for this probe follow simple trends as a function of mass number. These trends can be used to confidently determine Gamow-Teller strength distributions in nuclei for which the proportionality cannot be calibrated via beta-decay strengths. Although theoretical calculations in the distorted-wave Born approximation overestimate the data, they allow one to understand the main experimental features and to predict deviations from the simple trends observed in some of the transitions.

Coordination of microtubules and the actin cytoskeleton is important in osteoclast function, but calcitonin disrupts sealing zones without affecting microtubule networks.

Bone-resorbing osteoclasts form sealing zones and ruffled borders toward the bone surface. The sealing zone consists of a ring-like alignment of F-actin dots and surrounds the ruffled border, from which protons are secreted into the bone surface. Vacuolar-type proton ATPase (V-ATPase) in osteoclasts is a ruffled border-associated enzyme responsible for the proton secretion. We studied the interaction between microtubules and the actin cytoskeleton in osteoclasts. Confocal microscopic observation revealed that osteoclasts on glass coverslips, dentine slices and Osteologictrade mark discs formed the ring-like structure of F-actin dots, and microtubules overlapped the top of the F-actin dots. Osteoclasts cultured on dentine formed resorption pits within 48 h. The treatment of osteoclasts with cytochalasin D, an F-actin-depolymerizing reagent, induced perturbation of the microtubules in osteoclasts on glass and inhibited their pit-forming activity on dentine in a dose-dependent and reversible manner. Conversely, nocodazole, a microtubule-depolymerizing reagent, disrupted sealing zones and inhibited pit-forming activity of osteoclasts in a dose-dependent and reversible manner. V-ATPase showed a tendency to be localized inside sealing zones in osteoclasts. Treatment of osteoclasts with calcitonin induced both disruption of sealing zones and dispersion of V-ATPase to the whole area of the cytoplasm within 60 min. The microtubule networks in osteoclasts remained unchanged for 60 min even in the presence of calcitonin. These results suggest that coordination of the actin cytoskeleton and microtubules is important in the function of osteoclasts, but calcitonin selectively affects the actin cytoskeleton and induces the dispersion of V-ATPase without causing significant changes in the microtubules.

Genetic instability in lung cancer: concurrent analysis of chromosomal, mini- and microsatellite instability and loss of heterozygosity.

To investigate what kind of genetic instability plays important roles in lung carcinogenesis, we analyzed micro- and minisatellite instability, loss of heterozygosity (LOH) and chromosome instability in 55 cases of lung cancer, including, 10 squamous cell, 5 large cell, and 3 small cell carcinomas, and 37 adenocarcinomas. Analysis of minisatellite instability, the mechanism of which is different from microsatellite instability, has not been reported previously. Minisatellite instability was detected in only one case (1/55, 1.8%), and the frequency of microsatellite instability was low, being found only in three cases (3/55, 5.5%). In contrast, LOH, for at least in one locus, was observed in 27 cases (49.1%). In adenocarcinomas, the frequency of LOH was higher in poorly differentiated compared to more differentiated carcinomas. For chromosome instability, a similar correlation between differentiation grade and instability was observed in adenocarcinomas. And instability was more common in large cell and small cell carcinomas than in adenocarcinomas. Our analysis showed that chromosome instability and LOH, rather than mini- and microsatellite instability, play significant roles in the development of lung cancer.

Effects of calcitonin on the function of human osteoclast-like cells formed from CD14-positive monocytes.

Calcitonin inhibits bone-resorbing activity of osteoclasts. Expression of mRNA of calcitonin receptor (CTR) and its related proteins was examined in human osteoclasts and their progenitors. CD14-positive (CD14 + macrophages) in the monocytes prepared from human peripheral blood cells differentiated into macrophages (CD14 +) presence of macrophage colony-stimulating factor (M-CSF) or into osteoclast-like cells (OCLs) in the presence of M-CSF plus receptor activator of NFkappaB ligand. CD14 macrophages expressed mRNA of CTR-like receptor (CRLR), receptor activity modifying protein (RAMP) 1, RAMP2, and RAMP3, but not CTR. In contrast, OCLs expressed mRNA of CTR but not CRLR or RAMPs. Human OCLs cultured on dentine slices formed actin rings (corresponding to clear zones) and resorption pits on the slices. Calcitonin disrupted actin rings and inhibited the pit-forming activity of OCLs. CTR is known to couple to cAMP-dependent protein kinase (PKA) and protein kinase C (PKC). The effect of calcitonin on actin ring disruption was partially blocked by adding H-7, an inhibitor of both PKA and PKC. Both forskolin, an activator of PKA, and phorbol myristate, an activator of PKC, disrupted actin rings in OCLs. These results suggest that both PKA- and PKC-mediated signals are involved in calcitonin-induced inhibition of human OCL function.

Genetic manipulation and functional analysis of cAMP signalling in cardiac muscle: implications for a new target of pharmacotherapy.

Adenylate cyclase is a membrane-bound enzyme that catalyses the conversion of ATP into cAMP upon activation of cell-surface G-protein-coupled receptors, such as beta-adrenergic receptors, and initiates a cascade of phosphorylation reactions within the cell. Type 5 adenylate cyclase is a major isoform in the heart as well as in the striatum of the brain. Mice with a disrupted type 5 adenylate cyclase gene exhibited normal cardiac function under basal conditions, but a decreased response to isoprenaline stimulation. When mice were subjected to pressure overload stress with aortic banding, they developed cardiac hypertrophy, but with a significant reduction in the number of apoptotic cardiac myocytes as well as preserved cardiac function. When type 5 adenylate cyclase activity was inhibited pharmacologically, by the use of a novel P-site inhibitor with enhanced selectivity for this isoform, there were no changes in cardiac myocyte contractility, but the development of cardiac myocyte apoptosis induced by isoprenaline stimulation was effectively prevented. These results indicate that type 5 adenylate cyclase may serve as a better target of pharmacotherapy to prevent the development of cardiac myocyte apoptosis and thus failure in response to various cardiac stresses.

The Tokyo subway sarin attack--lessons learned.

The sarin gas attack in the Tokyo subway system is reviewed from a clinical toxicology perspective. Based on the lessons learned from this attack, the following areas should be addressed on a global scale. First, an adequate supply of protective equipment is required, including level B protective equipment with a pressure demand breathing apparatus. In addition, a system should be established that enables a possible cause to be determined based on symptoms, physical findings, general laboratory tests, and a simple qualitative analysis for poisonous substances. If an antidote is needed, the system should enable it to be administered to the victims as quickly as possible. Preparation for a large-scale chemical attack by terrorists requires the prior establishment of a detailed decontamination plan that utilizes not only mass decontamination facilities but also public facilities in the area. A system should be established for summarizing, evaluating, and disseminating information on poisonous substances. Finally, a large-scale scientific investigation of the Tokyo sarin attack should be conducted to examine its long-term and subclinical effects and the effects of exposure to asymptomatic low levels of sarin.

Gefitinib treatment affects androgen levels in non-small-cell lung cancer patients.

Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR, HER1/ErbB1) tyrosine kinase, has been shown to have clinical activity against non-small-cell lung cancers (NSCLCs), especially in women nonsmokers with adenocarcinomas. The aim of the present study was to clarify the relationship between androgen levels and gefitinib treatment in patients with advanced NSCLCs. Sera from 67 cases (36 men and 31 women) were obtained pretreatment and during treatment with gefitinib monotherapy (days 14-18) for examination of testosterone, dehydroepiandrosterone sulphate (DHEA), and dehydroepiandrosterone sulphate (DHEAS) levels. Testosterone and DHEA during treatment were significantly lower than the pretreatment values in both women and men, and the DHEAS levels during treatment were also significantly lowered in women. Gefitinib treatment significantly suppressed androgen levels, especially in women who had no smoking history. In addition, hormone levels in women responding to gefitinib were significantly lower during the treatment than in women who did not respond. Gefitinib-associated decrease in serum androgen levels may play a role in its clinical efficacy.

Vestibular function and vasopressin.

OBJECTIVE: To investigate the relation between the vestibular system and vasopressin (AVP). MATERIAL AND METHODS: We examined the effects of electrical and caloric vestibular stimulation on plasma AVP levels in anesthetized rats. Plasma AVP levels of patients with intractable Ménière's disease who were subjected to endolymphatic drainage and steroid instillation surgery (EDSS) or intratympanic gentamicin (GM) injection were measured before and after these interventions. RESULTS: Electrical vestibular stimulation increased plasma AVP levels in a current intensity-dependent manner. Plasma AVP levels were also increased by caloric stimulation with cold water. Plasma AVP levels decreased rapidly after EDSS, and were maintained at a low level even 6-12 months following EDSS or intratympanic GM injection. CONCLUSIONS: Vestibular activation or inhibition-induced imbalance of intervestibular activities increased plasma AVP levels in rats. Therefore, vestibular disorder would seem to increase plasma AVP and thus worsen endolymphatic hydrops. EDSS rapidly decreased plasma AVP and would seem to reduce hydrops. Inhibition of vertigo spells by EDSS or intratympanic GM injection would reduce a possible stress response, resulting in a decrease in plasma AVP levels a long time after the treatments. This resultant decrease in AVP would beneficially inhibit the formation and/or maintenance of hydrops and thus prevent vertigo spells.