[Challenges in diagnosing familial Mediterranean fever: exploring atypical clinical features. Clinical case].

This clinical case series presents descriptions of 3 patients with familial Mediterranean fever (FMF) who have atypical manifestations and abnormal inheritance mechanisms in terms of Gregor Mendel's laws. Although molecular genetic testing can help with disease diagnosis, it is not always conclusive. The primary need for genetic testing in atypical cases is to explain the mechanism of inflammation and to select the optimal therapy. These clinical observations demonstrate the changes in the spectrum of phenotypic manifestations of FMF in the context of the widespread introduction of molecular genetic methods.

[Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis].

AIM: To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). MATERIALS AND METHODS: Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). RESULTS: The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. CONCLUSION: Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

[History of the study of amyloidosis: from the Rokitansky's theory to the present day].

In the history of amyloidosis studying the concept of liquids dyscrasia has been predominated and finally it is resulted in accepting a serum protein-precursor as a leading amyloidogenic factor in the disease pathogenesis. Consequently basic diagnostic and treatment strategy was aimed to find and eliminate this protein from the blood and this approach evidenced high effectiveness in most frequent AA and AL-amyloidosis characterized with anomaly high levels of precursors in the blood. At the same time there are less frequent and slower progressing inheritant forms of systemic amyloidosis including transthyretin induced, which are less depending on amyloidogenecity of amyloid precursor and because of that, in example, the effectiveness of transthyretin stabilizers or blockers of its synthesis is limited comparing with the precursor elimination in AA or AL. Developed in the middle of XX century a theory of local synthesis by macrophages is more preferable to describe the pathogenesis of these forms. And modern proteome analysis using give rise to confirm the key meaning of macrophage in the amyloidogenesis and proves necessity to know deeply mechanisms of macrophagial autophagia - basic tool of maintaining intracellular protein homeostasis. That is why it is difficult to hope on high effectiveness of chemical amyloid solvents in vivo, which being under macrophages regulation never could realize its chemical activities.

[Lupus nephritis in the XXI century].

Lupus nephritis (LN) is the most common organ lesion in systemic lupus erythematosus (SLE), developing in 4050% of patients. Due to immunosuppressive therapy, the survival of patients with SLE has increased significantly over the past 50 years, and the proportion of severe kidney damage in the death structure has decreased. However, LN relapses and complications of immunosuppression, accelerated atherogenesis, concomitant diseases lead to the accumulation of organ damage and an increased risk of death. The article consideres the place of kidney damage in the SLE, the risk factors for LN development, the main renal histopathological changes, it identifies a number of issues that need to be addressed to optimize treatment and improve LN long-term outcomes, including, the revision of pathogenetic therapy regimens with restriction of glucocorticosteroids and prescribing drugs with steroid-sparing activity, the integration of new drugs for LN treatment, wider use of modern nephroprotection capabilities.

Methods for calculating the stereotaxic coordinates of rat brain structures by pixel coordinates of the image obtained by confocal and two-photon laser scanning microscopy.

BACKGROUND: There is a challenge to determine stereotaxic coordinates of a target structure with the accuracy, comparable to their size, when imaging the rat brain through cranial windows using confocal (multiphoton) microscopy in vivo. Some methods based on the estimation of the linear displacement from the intersections of the cerebral vessels are most often used for these purposes, but their accuracy can be improved. NEW METHOD: A new method for converting pixel coordinates of points of interest on an image obtained in two-photon microscopy into stereotaxic ones using quadratic approximation with L2 regularization has been developed. A comparative analysis of several methods for converting pixel coordinates into stereotaxic ones was carried out. The current study is aimed to select a method which minimizes the error of coordinate conversion within the a priori specified threshold value. RESULTS: A method for determining the stereotaxic coordinates of each pixel in an image obtained by laser scanning in two-photon and / or confocal modes with an accuracy of several tens of microns is proposed. COMPARISON WITH EXISTING METHOD(S): It is shown that the error probability of the most common method based on calculating the points of interest coordinates as displacements relative to the selected vessels intersections can be reduced by using the quadratic approximation with L2 regularization. Our proposed method allows us to improve the accuracy of determining the coordinates of points of interest on 10-30 µm. CONCLUSIONS: The proposed approach will be useful in research where precise positioning of microelectrodes, sensors, etc. for implantation in specified brain structures or groups of neurons determined by functional mapping is required.

[The balance of proinflammatory cytokines and Treg cells in chronic glomerulonephritis].

Chronic glomerulonephritis (CGN) is a disease with a steadily progressing course, which is based on inflammation with the activation of immune cells. The severity of the inflammatory reaction in the kidney tissue is determined by the balance of locally pro-inflammatory factors and protective mechanisms, which include anti-inflammatory cytokines and T-regulatory lymphocytes (Treg). The study of processes that can modulate the severity of inflammation in the kidney is of particular interest for understanding the basic patterns of CGN progression. AIM: To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS). MATERIALS AND METHODS: The study included 98 patients with CGN 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR60 ml/min/1.73 m2 was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm2 area). RESULTS: In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine. CONCLUSION: An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.

[Successful treatment of a rare variant of mesangioproliferative glomerulonephritis with IgM deposits with Cyclosporin A].

We present a case with a rare variant of glomerulonephritis, IgM nephropathy, which occurs mainly with nephrotic syndrome. The clinical features of this variant of kidney damage are characterized; the pathogenetic and the transformation of this form of nephritis into focal segmental glomerulosclerosis are discussed. The development of severe nephrotic syndrome at the beginning of the disease, the formation of secondary steroid resistance have confirmed this hypothesis and have justified the treatment with cyclosporin A aimed at the recovery of the function of the podocyte with remission of nephritis.

A simulated geomagnetic storm unsynchronizes with diurnal geomagnetic variation affecting calpain activity in roach and great pond snail.

It has been suggested that geomagnetic storms could be perceived by organisms via disruption of naturally occurring diurnal geomagnetic variation. This variation, in turn, is viewed by way of a zeitgeber for biological circadian rhythms. The biological effects of a geomagnetic storm, therefore, could depend on the local time of day when its main phase occurs. We have assessed calpain activity in tissues of roach (Rutilus rutilus) and great pond snail (Limnaea stagnalis) after exposure to a simulated geomagnetic storm, reproduced at different times of day, in order to evaluate this hypothesis. Significant decrease in calpain activity was observed in organisms exposed to the simulated geomagnetic storm whose main phase, and initial period of a recovery phase, did not coincide with the expected peak of diurnal geomagnetic variation. The results obtained are considered an experimental confirmation of the aforementioned hypothesis. Improvement of a correlative approach for the assessment of biological effects of geomagnetic activity can be achieved by considering information on the synchronization of geomagnetic storm's main phase with diurnal geomagnetic variation.

Activity of Metabolic Enzymes in Farmed Rainbow Trout Oncorhynchus mykiss Walb. Affected by Bacterial Septicemia: The Effect of Food Additives.

The effect of food additive including antioxidant dihydroquercetin and polysaccharide arabinogalactan on the activity of metabolic enzymes in muscles and liver of artificially grown rainbow trout Oncorhynchus mykiss affected by bacterial infection was investigated. The results of the study indicated an increase in the resistance of trout to the action of bacterial infection with the enrichment of the diet with the studied bioactive components, apparently mediated, among other factors, by the activation of metabolic pathways of synthesis of energy and reducing equivalents.

[Low protein diet with essential amino acids ketoanalogues combination can affect serum FGF-23 and Klotho levels in chronic kidney disease 3b-4 stages patients: randomized pilot study].

Protein restriction diet (PRD) with ketoanalagues of essential amino acids (KA) combination can improve of chronic kidney disease (CKD) course while, the precise mechanisms of PRD + KAA action in CKD are not known yet. We have conducted a prospective, randomized, controlled study of PRD and KAA patient's group in compare with PRD without KAA group in regarding to serum Klotho and FGF-23 levels in patients with CKD. MATERIALS AND METHODS: The study included 79 CKD 3b-4 stages patients, non - diabetic etiology, used PRD (0.6 g/kg/day). The patients were randomized in two groups: 42 patients, received PRD + KAA (Group 1) and 37 patients continued the PRD without KAA (Group 2). Serum FGF-23 (Human FGF-23 ELISA kit with antibodies to native FGF-23 molecule, Merk Millipore MILLENZFGF-23-32K), Klotho (Human soluble Klotho with antiKlotho monoclonal antibodies, IBL-Takara 27998-96Well) levels, as well as instrumental examination: bioimpedance analysis [assess of muscle body mass (MBM), fat body mass (FBM), body mass index (BMI) and others]; sphygmography [assess of augmentation (stiffness) indices (AI), central (aortal) blood pressure (CBP) by «Sphygmacor¼ device]; as well as echocardiography [assess of cardiac (valvular) calcification score (CCS) and left ventricular myocardium mass index (LVMMI)], were studded in addition to conventional examination. RESULTS AND DISCUSSION: To the end of 14th month of the study the PRD group reached a body mass index (BMI) decrease (p=0.046), including MBM in men (p=0.027) and woman (p=0.044). In addition, higher FGF-23 (p=0.029), and lower Klotho (p=0.037) serum levels were revealed in the PRD group compared to the PRD+KAA group as well as the increase in AI (p=0.034), CCS (p=0.048), and LVMMI (p=0.023). CONCLUSION: Use of PRD + KAA provides adequate nutrition status and more efficient correction of FGF-23 and Klotho imbalance in CKD progression that may contribute to alleviation of both cardiovascular calcification and cardiac remodeling in CKD. Importantly, a prolonged PRD use without supplementation of KAA may lead to malnutrition signs.

[Clinical and pathologic features of nephropathy with C1q deposits].

AIM: To determine the frequency, clinical and morphological features of a nephropathy with C1q deposits in chronic glomerulonephritis adult patients. MATERIALS AND METHODS: 296 specimens of kidneys of patients with a chronic glomerulonephritis (CGN) from 2014 for 2018 were analyzed. At the first step, specimens with C1q deposits in glomeruli revealed by immunofluorescent method were chosen. Lupus nephritis and primary membranoproliferative glomerulonephritis were exclusion criteria. At the second step, the retrospective analysis of the clinical characteristics was carried out. RESULTS AND DISCUSSION: Deposits of C1q in kidneys at 12 of 296 (4.05%) CGN were revealed, m:f ratio 2:1. Average age of the beginning of a disease was 32.1±14.7 years. At a morphological research in 8 membranous nephropathy (MN), in 2 mesangioproliferative glomerulonephritis (MesPGN), in 2 - nephrosclerosis was revealed. Among 12 patients in 5 the disease debuted a nephrotic syndrome, at the others - a proteinuria from 0.5 to 4.0 g/days with the subsequent formation of a nephrotic syndrome. In 5 of 12 patients the disease was characterized by a favor course with preserved kidney function. At 7 patients at the time of inspection decrease in function of kidneys [glomerular filtration rate (eGFR) 31 (30-34) ml/min] was noted. 5 had slow progressing of a renal failure. 2 of 12 progressed to renal failure (eGFR to 19 and 24 ml/min) within a year. CONCLUSION: Deposits of C1q in kidney were revealed in 4.05% of biopsy specimens in CGN. The most frequent morphological form was the membranous nephropathy. The clinical course was characterized by a nephrotic syndrome, more than at a half of patients - with renal dysfunction.

[Modern approaches to the detection of monoclonal gammopathy of undetermined significance (MGUS) in patients with kidney diseases].

Monoclonal gammopathy (MG) is not only the state preceding of hematological neoplasms, but also associated with non - hematological diseases, in particular kidney damage. AIM: To assess the diagnostic value of "Freelite" methods in addition to electrophoresis (EF) and immunofixation (IF) of serum and urine proteins for detecting MG in patients with kidney diseases. MATERIALS AND METHODS: 87 patients with kidney damage, in which MG was established using the method of electrophoresis of serum proteins (EF), immunofixation (IF) and the method of free light chains determination - FLC "Freelite" were selected. The diagnostic value of three - component serum panel was compared with EF and IF. RESULTS AND DISCUSSION: AL-amyloidosis with kidney involvement was diagnosed in 41% patients, cryoglobulinemic glomerulonephritis (cryo GN) - in 18%, chronic glomerulonephritis (CGN) - in 35%, also there was small number of patients with light chain disease and cast - nephropathy. Determination of MG using EP was possible only in 38 (44%). Adding to the serum electrophoretic methods instead of the "Freelite" method, the urine EF and IF reduced the number of missed patients with monoclonal gammopathy from 24 (27%) to 11 (13%), including in the subgroup of patients with AL-amyloidosis but did not reach the sensitivity of the three - component serum screening panel. In 10 (11.5%) MG was represented only by intact mIg with one type of light chain, either κ or λ. Most often - in 25% of patients, intact monoclonal gammopathy was observed in HCV (+) cryo GN. A combination of intact mIgM, mIgG or mIgA with mFLC, was detected in 37 (42.5%). In almost half (46%) of the patients, only mFLC was detected - an abnormal κ/λ ratio. CONCLUSION: The serum screening panel EF + IF + "Freelite" spreads the low - grade monoclonal gammopathy recognition (MGUS) and should be included in the algorithm of examining patients with kidney disease.

[Serum troponin-I as a marker of fibroblast growth factor-23 (FGF-23) cardiotoxic effect, in patients with chronic kidney disease].

AIM: It has been established that an increased fibroblast growth factor (FGF-23) serum levels significantly contribute to the heart and blood vessels remodeling in patients with chronic kidney disease (CKD). But the precise mechanisms of the FGF-23 cardiac effect are currently being actively studied. At the same time, it is believed that the cardiac effects of FGF-23 may be due to the increasing deficit of Klotho protein as CKD progresses. In parallel with these changes, a number of studies indicate the persistence of the detectable troponins serum levels in CKD patients, even in the absence of clear clinical manifestations of cardiovascular diseases (CVD). The aim of the study was to confirm / exclude the existence of a causal relationship between elevated FGF-23, reduced Klotho and elevated troponin-I (as the most specific troponin in CKD). MATERIALS AND METHODS: The study included 130 CKD stages 1-5D patients without clinically pronounced symptoms of СVD (Coronary artery disease, CCS class 2-4, Chronic heart failure, NYHA 24, myocarditis, pericarditis, arrhythmias), as well as the severe arterial hypertension (BP >160/90 mm Hg), according to the laboratory and instrumental methods of examination. The selected group of patients was studied: serum levels of FGF-23 (Human FGF-23 ELISA kit), Klotho (Human soluble Klotho with antiklotho monoclonal antibodies), troponin-I (high - sensitive assay), and also data from instrumental examination methods: electrocardiography (ECG), echocardiography (left ventricular myocardial mass index (LVMI), cardiac (valvular) calcification score (CCS) using a semi - quantitative point scale), sphygmagraphy (augmentation (stiffness) indices of vessels (AI), pulse wave velocity (PWV), central (aortic) blood pressure (CBP), blood supply of subendocardium (BSE) - using "Shygmacor" device (Australia)). RESULTS AND DISCUSSION: The changes in serum levels of FGF-23, Klotho and troponin-I (Tr-I) depended on the stage of CKD. The following correlations were identified: FGF-23 and: Tr-I (r=0.601; p.

[Hepatitis C virus - related cryoglobulinemic vasculitis with renal involvement current possibilities of diagnostic and treatment].

The extrahepatic manifestations of HCV infections, which include mixed cryoglobulinemia (MC), are important for prognosis and determination of the treatment options of these patients. Currently, mixed MC type II is considered as a specific marker of chronic HCV infection. Kidney damage is one of the severe, often determining a prognosis of extrahepatic manifestation of HCV-associated cryoglobulinemic vasculitis. The review discusses the current diagnostic approaches to cryoglobulinemic GN, as well as perspectives for improving antiviral and pathogenetic therapy.

The role of podocytes dysfunction in chronic glomerulonephritis progression.

In the review, the mechanisms of podocytes damage underlying the development of proteinuria and progression of glomerulosclerosis in chronic glomerulonephritis are discussed in detail. The results of experimental and clinical studies are presented. Under the different immune and non-immune factors the podocytes form a stereotyped response to damage consisting in the reorganization of the actin cytoskeleton, foot process effacement, the detachment of podocytes from the glomerular basement membrane, and the appearance of specific podocyte proteins and whole cells (podocyturia) in the urine. Massive podocyturia in a limited proliferative capacity of podocytes leads to reduce their total count in the glomerulus (podocytopenia) and the development of glomerulosclerosis. The authors describe the line of markers of the podocyte injury and invasive and non-invasive methods of their assessment. In addition, the relationship of podocyturia level with proteinuria and renal dysfunction are discussed, the prospects of assessment the podocyte proteins in urine for assessing of glomerular damage severity and glomerulosclerosis risk are examined.

[Degradation of skeletal muscle protein during growth and development of salmonid fish].

Published data and the results of the authors' own studies on the role of intracellular proteolytic enzymes and the metabolic and signaling processes regulated by these enzymes at certain stages of growth and development of salmonid fishes are analyzed in the present review. The major pathways of intracellular proteolysis relying on autophagy, proteasome activity, and calpain activity are considered, as well as the relative contribution of these pathways to proteolysis in skeletal muscle of the fish. Skeletal muscle accounts for more than half of the weight of the fish and undergoes the most significant changes due to the action of anabolic and catabolic signals. Special attention is paid to the intensity of protein degradation during the active growth period characterized by a high rate of protein synthesis and metabolism in fish, as well as to protein degradation during the reproductive period characterized by predomination of catabolic processes in contrast to the growth period. Skeletal muscle plays a unique role as a source of plastic and energy substrates in fish, and, therefore, the process of muscle protein degradation is regarded as a key mechanism for the regulation of growth intensity in juvenile salmon and for maintenance of viability and reproductive capacity of salmonid fish during the maturation of gametes, starvation, and migration related to spawning. The possibility of using a set of parameters of intracellular proteolysis to characterize the early development of salmonids is demonstrated in the review.

[Analysis of results of drug therapy for symptomatic multiple myeloma].

Drug therapy for symptomatic multiple myeloma is comparable for both sexes in its effectiveness and safety. A 3-year event-free survival is comparable in men and women; overall survival in men is lower than in women.

The role of lysosomal proteinases and estradiol in neurodegeneration induced by beta-amyloid.

Activation of lysosomal degradation process in nervous tissue may be neuroprotective. One of the factors that may influence on expression of lysosomal proteinases is the sex hormone, estradiol (E2). In this regard the expression of lysosomal proteinases after intracerebral injection of beta-amyloid peptide (Aß) was investigated as well as the neuroprotective effect of E2 in Aß-induced neurodegeneration. Intracerebral injection of Aß was shown to cause the significant increase in expression of cathepsin D in rat hippocampus and cerebral cortex. On the background of Aß intoxication, E2 treatment resulted in further increase in cathepsin D gene expression in hippocampus region and in its lowering to the control level in cerebral cortex. It was demonstrated for the first time that neuroprotective effect of E2 may be mediated by cathepsin D up-regulation.

[Acute glomerulonephritis in the 21-st century].

The paper discusses the specific features of the current course of acute glomerulonephritis, the spectrum of its etiological factors, and clinical manifestations. The factors influencing the course and outcomes of acute glomerulonephritis, including the risk of its progression to chronic kidney disease, are specially depicted.

[BIOCHEMICAL RESPONSE OF BLUE MUSSELS MYTILUS EDULIS L. FROM THE WHITE SEA TO RAPID TEMPERATURE CHANGES].

The effect of a rapid temperature change on the biochemical status of blue mussels Mytilus edulis L. from the White Sea was studied under conditions of aquarium experiment. It is shown that modifications of the composition of reserve and structural lipids and their fatty acids, of the activity of lysosomal enzymes (ß-glucosidases, cathepsins B and D), of calcium-dependent proteases of cytocol (calpains) and of the enzyme of the second phase of biotransformation of xenobiotics - glutathione-S-transferase, reflect an unspecific compensatory reaction of bivalves to stress action of environmental factors and indicate reconstruction of blue mussel metabolism as early as within first hours of temperature change. The initial high level of glutathione-S-transferase activity in control blue mussels as well as an increase of glutathione concentration in the course of experiment may facilitate successful exit of mussels from the state of reduced metabolism.