Predictors of receiving a diagnosis, referral and treatment of depression in people on antiretroviral therapy in South African primary care: a secondary analysis of data from a randomised trial.

OBJECTIVE: To describe the receipt of a diagnosis, referral and treatment for depression in people receiving antiretroviral therapy (ART), with depressive symptoms and attending primary care clinics in South Africa, and investigate factors associated with receiving these components of care. METHODS: This is a secondary analysis of data from a randomised controlled trial of an intervention intended to improve detection and treatment of depression in primary care patients receiving ART. In this analysis, we combined cross-sectional and longitudinal data from the intervention and control arms. Using regression models and adjusting for intra-cluster correlation of outcomes, we investigated associations between socioeconomic characteristics, depressive symptoms, stress, disability and stigma, and receipt of a diagnosis, referral and treatment for depression. RESULTS: Of 2002 participants enrolled, 18% reported a previous diagnosis of depression by a healthcare worker and 10% reported having received counselling from a specialist mental health worker. Diagnosis, referral and counselling during the follow-up period were appropriately targeted, being independently more frequent in participants with higher enrolment scores for depressive symptoms, stress or disability. Participants with higher stigma scores at enrolment were independently less likely to receive counselling. Severe socio-economic deprivation was common but was not associated with treatment. CONCLUSION: While the receipt of a diagnosis, referral and treatment for depression were uncommon, they seemed to be appropriately targeted. Socio-economic deprivation was not associated with treatment.

OBJECTIF: Décrire la réception d'un diagnostic, de l'orientation et du traitement pour la dépression chez les personnes recevant un traitement antirétroviral (ART), présentant des symptômes dépressifs et fréquentant des cliniques de soins primaires en Afrique du Sud, et étudier les facteurs associés à la réception de ces éléments de soins. MÉTHODES: Il s'agit ici d'une analyse secondaire des données d'un essai contrôlé randomisé d'une intervention destinée à améliorer la détection et le traitement de la dépression chez les patients sous ART dans les soins primaires. Dans cette analyse, nous avons combiné les données transversales et longitudinales des bras d'intervention et témoin. En utilisant des modèles de régression et en ajustant la corrélation intra-grappes des résultats, nous avons étudié les associations entre les caractéristiques sociodémographiques, les symptômes dépressifs, le stress, l'invalidité et la stigmatisation, et la réception d'un diagnostic, d'une orientation et d'un traitement pour la dépression. RÉSULTATS: Sur 2.002 participants inscrits, 18% ont déclaré un diagnostic antérieur de dépression par un agent de santé et 10% ont déclaré avoir reçu des conseils d'un agent spécialisé pour la santé mentale. Le diagnostic, l'orientation et le conseil pendant la période de suivi ont été ciblés de manière appropriée, étant indépendamment plus fréquents chez les participants ayant des scores d'inscription plus élevés pour les symptômes dépressifs, le stress ou l'invalidité. Les participants ayant des scores de stigmatisation plus élevés à l'inscription étaient indépendamment moins susceptibles de recevoir des conseils. La privation socioéconomique sévère était courante mais n'était pas associée au traitement. CONCLUSION: Bien que la réception d'un diagnostic, l'orientation et le traitement de la dépression soient rares, ils semblaient bien ciblés. La privation socioéconomique n'était pas associée au traitement.

Testosterone-mediated activation of androgenic signalling sustains in vitro the transformed and radioresistant phenotype of rhabdomyosarcoma cell lines.

PURPOSE: Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in childhood, rarely affects adults, preferring male. RMS expresses the receptor for androgen (AR) and responds to androgen; however, the molecular action of androgens on RMS is unknown. METHODS: Herein, testosterone (T) effects were tested in embryonal (ERMS) and alveolar (ARMS) RMS cell lines, by performing luciferase reporter assay, RT-PCR, and western blotting experiments. RNA interference experiments or bicalutamide treatment was performed to assess the specific role of AR. Radiation treatment was delivered to characterise the effects of T treatment on RMS intrinsic radioresistance. RESULTS: Our study showed that RMS cells respond to sub-physiological levels of T stimulation, finally promoting AR-dependent genomic and non-genomic effects, such as the transcriptional regulation of several oncogenes, the phosphorylation-mediated post-transductional modifications of AR and the activation of ERK, p38 and AKT signal transduction pathway mediators that, by physically complexing or not with AR, participate in regulating its transcriptional activity and the expression of T-targeted genes. T chronic daily treatment, performed as for the hormone circadian rhythm, did not significantly affect RMS cell growth, but improved RMS clonogenic and radioresistant potential and increased AR mRNA both in ERMS and ARMS. AR protein accumulation was evident in ERMS, this further developing an intrinsic T-independent AR activity. CONCLUSIONS: Our results suggest that androgens sustain and improve RMS transformed and radioresistant phenotype, and therefore, their therapeutic application should be avoided in RMS post puberal patients.

Laparoscopic versus open appendectomy in the management of acute appendicitis in children: a multicenter retrospective study.

AIM: Acute appendicitis is one of the most common indications for emergency surgery in children. Open appendectomy (OA) has been the gold standard treatment for over 100 years. In the last three decades, the introduction of minimally invasive techniques, such as laparoscopic appendectomy (LA) and transumbilical laparoscopically assisted appendectomy (TULAA), has changed the approach to the disease. However, there is still no agreement with benefits of these new therapeutic options, especially in children. The aim of this retrospective study is comparing the outcomes of OA, LA and TULAA in the paediatric patient. METHODS: Children suffering from acute appendicitis were treated with LA or TULAA in the Department of Paediatric Surgery and with OA in the Department of General Surgery. Data were abstracted from database of both centers' archives. Operator, operating time, length of hospitalization (LOH), intra- and postoperative complications and histological finding were analyzed. RESULTS: We recruited 196 patients: 46 treated with LA, 62 with TULAA and 88 with OA. Operative time was significantly shorter in OA. The three techniques had the same incidence of intraoperative and postoperative complications. The incidence of wound infection was higher with the TULAA approach. LOH was significantly shorter in the TULAA group. There was no correlation between LOH and histological finding. CONCLUSION: We demonstrated that LA, TULAA and OA are similar in most respects and are equally safe modalities in paediatric patients. Further randomized controlled studies are necessary.

Vitamin D protects human endothelial cells from H2O2 oxidant injury through the Mek/Erk-Sirt1 axis activation.

Endothelium homeostasis alterations govern the pathogenesis of cardiovascular diseases. Several studies show that vitamins anti-oxidant proprieties rescue the endothelial functions adversely affected by oxidative stress in several diseases. We investigated the vitamin D anti-oxidant potential in human endothelial cells exposed to H2O2 oxidative stress. Vitamin D protected endothelial cells against H2O2 oxidative stress counteracting the superoxide anion generation, the apoptosis and blocking the extrinsic caspase cascade by positively controlling phospho-active ERKs level. MEKs/ERKs inhibitor U0126 reverted the vitamin D anti-oxidant effects. Characterizing the vitamin D downstream effector, we found that vitamin D up-regulated SirT-1 and reverted the SirT-1 down-regulation induced by H2O2. ERKs activation by vitamin D strictly correlated with SirT-1 protein accumulation since both MEKs/ERKs inhibition and ERK1/2 silencing decreased SIRT-1. SirT-1 inhibition by Sirtinol reverted the vitamin D anti-oxidant effects. Thus, vitamin D significantly reduced the endothelial malfunction and damage caused by oxidative stress, through the activation of MEKs/ERKs/SirT-1 axis.

[Multifactorial prognostic analysis in the surgical treatment of well differentiated thyroid neoplasms]. / Analisi prognostica multifattoriale nel trattamento chirurgico dei tumori differenziati della tiroide.

BACKGROUND: Although in recent years our knowledge of pathogenesis and natural history of thyroid cancer has widely increased, there is not accordance among authors in the field of surgical treatment of well-differentiated tumours. In fact the extension of the tumour resection and modality of cervical lymph-nodes dissection show questions not easy to answer. METHODS: From 1985 to 1994, in our Surgical Institute, 128 cases of well-differentiated thyroid cancer, out of 1346 nodular thyreopathies, were operated on. We have considered some factors as anamnestic thyreopathy, familiarity, symptoms, US and scyntigraphic factors, fine-needle aspiration cytology and surgical option. The surgical treatment consisted of 99 total thyroidectomies (with or without cervical lymph-nodes dissection) and 18 lobus-isthmectomies. Surgical morbidity was 0.7% for permanent vocal cords palsy, 9.3% for transient hypoparathyroidism and 1.4% for permanent hypoparathyroidism. RESULTS: The 5.8-year survival rate was 92.9%. Fifty-four patients were in Stage I, 35 patients in Stage II, 27 in stage III and 4 in Stage IV. Histological patterns showed the prevalence of papillary type (63.3%) over follicular type (36.7%). CONCLUSIONS: The aggressive surgical approach in well-differentiated thyroid tumours, supported by complementary postoperative therapies, leads to a good control of the disease

Concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expanders after mastectomy for breast cancer.

BACKGROUND: Immediate breast reconstruction (IBR) by means of skin expander is currently one of the most widely used methods of breast reconstruction in mastectomized patients. However, given that many breast cancer patients usually receive adjuvant chemotherapy, the adoption of IBR raises new questions concerning possible cumulative toxicity. The present study reports our experience in the use of concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expander after mastectomy for breast cancer and the acute cumulative toxicity of the treatments. METHODS: We evaluated a consecutive series of 52 breast cancer patients who have received IBR by skin expander after radical mastectomy and adjuvant chemotherapy concurrently during skin expansion between 1995 and 1998 (IBR/CT group). We identified two series of control patients treated during the same period: 51 consecutive patients undergoing radical mastectomy and IBR without adjuvant chemotherapy (IBR group) and 63 consecutive patients undergoing radical mastectomy and adjuvant chemotherapy without IBR (CT group). For each patient, we evaluated the incidence of surgical complications and chemotherapy's side effects and dose intensity. RESULTS: The interval between surgery and the start of expander inflation was similar in IBR/CT (range 0-19, median 5 days) and IBR groups (range 0-40, median 5 days) and the timing of inflation was not influenced by chemotherapy. The overall incidence of surgical complications in patients undergoing IBR was low: seroma in eight cases, infection in one, skin necrosis in one, expander rupture in two and erythema in three. There were no statistically significant differences in the distribution of complications between the IBR/CT and IBR groups. The dose intensity of chemotherapy was similar between IBR/CT and CT groups, with a median dose intensity of 96% and 95% of the projected dose, respectively. The only statistically significant difference in terms of chemotherapy side effects (p = 0.03) was that stomatitis was more frequent and intense in the CT than in the IBR/CT group. CONCLUSIONS: Concurrent treatment with IBR and adjuvant chemotherapy appears feasible and safe, it does not increase acute surgical complications or chemotherapy side effects, and does not require any changes in dose intensity or the timing of inflation.

Statewide replication of predictive validation for the Multnomah Community Ability Scale.

The Multnomah Community Ability Scale is a 17 item instrument that case managers can use to rate levels of functioning for clients with severe mental illness. Prior work in a large urban community mental health center showed that the instrument predicted subsequent involuntary hospitalization. The current project involved some 2,487 clients of community mental health programs throughout Oregon. This replication study again showed that low scores on the instrument predicted subsequent psychiatric hospitalization.

Psychosocial integration of adolescents and young adults with thalassemia major.

UNLABELLED: The aim of this study was to explore the effect of thalassemia major on the psychosocial adjustment of adolescents and young adults. DESIGN: unmarried adolescent and young adult patients were asked to fill in an ad hoc questionnaire; a semi-structured interview exploring marriage and family life was done with married patients. SAMPLE: group A: 90 unmarried patients, 50% females and 50% males, aged 14-22 years. The control group was formed by 100 matched subjects; group B: 19 thalassemic married subjects, 6 males and 13 females, aged 28-45 years, 7 patients had children and 12 did not. RESULTS: group A: subjects with thalassemia had normal psychological and social development and scored better than their normal peers in tests investigating social adjustment, self-esteem and self-description. Moreover the family relationships of adolescents with thalassemia appeared to be stronger than those reported by normal controls; group B: the behavior of thalassemic couples did not differ from the one observed in non-thalassemic couples in the course of previous investigations. CONCLUSIONS: Our data shows that neither thalassemic adolescents nor thalassemic married, well-treated, young adults differ significantly from the healthy young people in their ability to cope with life's difficulties both in adolescence and marital life.

Who has the final say? Decisions on adolescent behaviour within the family

The transition to adolescence involves significant changes for the family. To date, research on these changes and how they occur has been restricted by lack of suitable measures. An instrument-the Perspectives on Adolescent Decision-Making Questionnaire-was designed for such research. It examines 21 issues which can lead to conflict. The instrument was completed by 500 Italian adolescents aged 13 and 15. Sensitivity to age and sex differences was examined, and perceptions of personal choice, parental feelings, conflict and normal patterns for adolescents were analysed. The instrument offers promising possibilities for more effective study of parent/offspring relationships during the adolescent period.

Enhanced expression of myogenic regulatory genes in aging skeletal muscle.

MyoD, myogenin, myf-5, and MRF4, belonging to the family of basic helix-loop-helix (bHLH) myogenic regulatory factors (MRFs), control muscle cell differentiation, in concert with other transcription factors such as MEF-2, yet their role in age-related skeletal muscle alteration has not been addressed. We here report that MyoD and myogenin transcripts are expressed at high levels in the hind limb muscles of newborn mice and their level of expression continuously declines throughout postnatal life to become virtually undetectable in the adult mouse. However, these transcripts are again expressed at high levels in the muscles of older mice. MRF4 transcript, on the other hand, is present at a constant level throughout the life span of the animal. Conversely, the expressions of myf-5 and MEF-2C, components of the autoregulatory loop for the activation of bHLH gene expression, conspicuously increase in adult and senile muscle. In order to establish whether these transcripts are functioning in the aged muscle we investigated the expression of bHLH inhibitory factor Id mRNA showing that it does not present significant changes during aging. Immunofluorescence analysis with an anti-myogenin antibody revealed nuclear accumulation of the protein in the muscle fibers of old, but not of adult, mice. Muscle-specific genes transactivated by MyoD and myogenin such as AChR, MLC, and MCK are also up-regulated during aging, albeit at a lower level. Significant changes in the size and ratio of type I/type II fibers are detectable in senile muscle. These findings show that all members of the MRF family are expressed to a high extent and are likely active in senile muscle. It is conceivable that these changes might operate as a compensatory mechanism in maintaining the expression of differentiated muscle products in senile muscle at a steady-state level.

Calcitonin down-regulates immediate cell signals induced in human osteoclast-like cells by the bone sialoprotein-IIA fragment through a postintegrin receptor mechanism.

Calcitonin (CT) is a peptide hormone that interacts with the cAMP-and phospholipase C-associated CT receptor subtypes. We investigated whether CT modulates the interaction of human tumoral osteoclast-like (GCT23) cells with a protein of the bone matrix, bone sialoprotein-II (BSP-II). Single GCT23 cells loaded with the intracellular Ca2+ indicator fura-2 were treated with the maximal active dose (300 micrograms/ml) of the 18-mer Arg-Gly-Asp (RGD)-containing BSP-IIA fragment, and the cytosolic free Ca2+ concentration ([Ca2+]i) was measured by dual wavelength microfluorometry. BSP-IIA stimulated an elevation in [Ca2+]i, consisting mainly of a peak, followed by a rapid return toward baseline. Pretreatment with CT induced a modest elevation of [Ca2+]i. However, CT significantly inhibited the response to BSP-IIA in a dose-dependent manner. Maximal inhibition (90% vs. untreated) was observed in the micromolar range. The intracellular mechanisms leading to this effect were investigated by pretreatment of GCT23 cells with the cAMP permeant analog, (Bu2)cAMP, and the protein kinase-C-activating agent, 12-O-tetradecanoylphorbol 13-acetate. Similar to CT, both agents inhibited the response to 300 micrograms/ml BSP-IIA. The effect induced by CT was specific, because an increase in the extracellular Ca2+ concentration, which is also known to inhibit bone resorption, failed to modify the ability of BSP-IIA to alter [Ca2+]i in GCT23 cells. To investigate whether the CT-induced alteration of BSP-IIA-dependent cell signals was due to a modification in the synthesis of cell surface receptors (integrins) for the extracellular matrix macromolecules, 1-h CT-treated [35S]methionine metabolically labeled GCT23 cell lysates were immunoprecipitated with anti-alpha 3-, -alpha v-, -beta 1-, and -beta 3-integrin subunit antibodies. Autoradiography demonstrated that 10(-7)-10(-6) M CT did not alter new synthesis of the alpha v beta 3 and the alpha 3 beta 1 receptors. Similarly, CT did not affect surface expression of these receptors, assessed by enzyme-linked immunosorbent assay. Finally, no alteration of the adhesion rate and spreading of GCT23 cells onto BSP-IIA-coated substrates was observed. This indicates that CT-induced down-regulation of immediate cell signals prompted by BSP-IIA in GCT23 cells is a postintegrin receptor event.

TPA-induced differentiation of human rhabdomyosarcoma cells involves dephosphorylation and nuclear accumulation of mutant P53.

Previous studies have shown that human rhabdomyosarcoma cells are induced to differentiate by TPA, in the absence of appreciable alterations of the muscle regulatory genes and their products (1). The question was addressed whether the tumor suppressor p53 could be a target of TPA action in these cells. Genomic analysis by a Polymerase Chain Reaction/Single-Strand Conformation Polymorphism (PCR/SSCP) and direct sequencing indicate the presence of a mutation in exon VII at codon 248 (C to T transition) and a loss of heterozygosity of p53 gene in human rhabdomyosarcoma cell line (RD). It is here shown that transcription of p53 mRNA strongly decreases in RD cells induced to growth arrest and differentiate by TPA treatment. In these cells immunoprecipitation and immunoblot analysis show that both synthesis and total cellular concentration of the protein are also reduced by TPA. Nevertheless nuclear p53 accumulation is at much higher extent, whereas 32P-orthophosphate labelling, followed by immunoprecipitation, demonstrates a decrease of phosphorylation of both cytoplasmic and nuclear p53. These results indicate that TPA causes a number of alterations of mutant p53, likely mediated through a protein kinase C dependent mechanism, which might impair the transforming ability of mutant p53 in growth-arrested and differentiating RD cells.

Paracrine stimulation of senescent satellite cell proliferation by factors released by muscle or myotubes from young mice.

The proliferative potential of satellite cells undergoes a dramatic decrease in the early postnatal period and a more modest but continuous decrease throughout the life span of the animal. To address the problem of the mechanism regulating this phenomenon and to understand whether it is causally linked to senile muscle atrophy, we studied the response of aged satellite cells to serum and to different growth factors. The data reported indicate a generalised reduction in the response to all mitogens tested, which could not be compensated for by increased concentrations of serum or growth factors. On the other hand, conditioned medium of differentiated myotubes from young mice exhibited a strong mitogenic action on aged satellite cells, while conditioned media of myotubes from old mice or from a variety of non-muscle cells were ineffective. Furthermore, saline extracts from muscle of young mice are also able to exert this mitogenic action. Saline extracts of muscle from old mice were poorly mitogenic for satellite cells from young mice, and not at all for satellite cells from old mice. These data indicate that paracrine interactions operate inside the muscle tissue and are probably required for the normal replicative behaviour of satellite cells. The failure of such interactions may be among the causes leading to age-related muscle hypotrophy.

The role of spontaneous portosystemic shunts in the course of orthotopic liver transplantation.

Spontaneous portosystemic shunts are commonly found in cirrhotic patients. Not yet established is their role after orthotopic liver transplantation (OLTx), especially when an increase in portal pressure develops, as during early acute rejection. In this study, 34 cirrhotic patients in a series of 70 OLTx are considered. Each patient had preoperative angiographic assessment, and, in 21 (62%), large spontaneous portosystemic shunts were evident. In 12 cases the shunts were not affected by the surgical procedure and were present during the postoperative period; in 9 the hepatectomy itself involved interruption of the shunts. The patient population was divided into two groups: patients with postoperative shunts (n = 12) and those without (n = 22). The two groups were similar in age, sex, Child's stage, transplantation variables, and number and grade of rejection episodes. However, mean transaminases (AST) values in the first 2 weeks were significantly higher levels in shunt versus nonshunt patients (421 +/- 335 vs 183 +/- 126; P less than 0.025), and this was even more evident when rejection occurred (626 +/- 375 vs 195 +/- 129; P less than 0.001). Furthermore, during an acute rejection reaction, three cases showed a true "steal phenomenon" through the large reopened shunts with ischemic damage to the grafts. The data indicate a possible detrimental effect of the spontaneous shunts on graft perfusion and suggest the prophylactic surgical interruption of the residual shunts during the transplantation.

Biliary complications in orthotopic liver transplantation: experience with a modified technique of duct-to-duct reconstruction.

Biliary complications are described as frequent causes of morbidity during the postoperative course of orthotopic liver transplantation (OLTx), even in recent papers. The authors report here on their experience with duct-to-duct anastomosis as their method of choice for biliary reconstruction in a consecutive series of 100 OLTx in adult patients. The original technique, as described by Starzl, was modified by the authors by performing a wide, longitudinal plasty of both the donor and recipient bile ducts, joined together with two polidioxanone running sutures, producing the effect of a side-to-side anastomosis. This technique was used in all procedures, even when a significant discrepancy was evident between the ducts (n = 10). Follow-up was completed in 100% of the patients for a period of 2-40 months (mean 13.1 months). Four major complications (4%) occurred including hepatic abscesses due to ascending cholangitis, T-tube dislocation, partial occlusion by a branch of the T-tube at the anastomotic site, and disruption of the bile duct after T-tube removal. In four other patients, transient abdominal pain followed removal of the stent. Neither strictures nor fistulas were observed. Choledochocholedochostomy on a T-tube stent represents, in our experience, the technique of choice for biliary reconstruction in OLTx. The procedure, as described in the present study, proved to be safe in preventing strictures and leakages and appears to be feasible in nearly 100% of all adult patients undergoing OLTx.

Male and female patterns in the discovery of sexuality during adolescence.

The present paper attempts to analyse the various factors which influence adolescents strategies in their efforts to cope with the problems related to pubertal and sexual development: the physiological changes, the social pressures engendered by family and cultural environment, and the personal meanings young boys and girls attribute thereto. The data came from 603 questionnaires and 60 interviews performed on Italian adolescents (both males and females, students and non-students) on the following issues: the awareness of physical maturation in the same and opposite sex; the significance of heterosexual relationships; the motivation for early sexual experiences; and their effects on personal identity. Significant differences concerning sex and level of schooling emerged with regard to the elaboration of the subject's psychosexual identity, motivation in the choice of partner and the precocity in the onset of sex life.

Spontaneous channel activity induced by tumor promoter TPA in chick myotubes.

Patch-clamp recordings were used to study the activation of ion channels in the cell membrane of cultured embryonic chick myotubes treated with the specific activator of protein kinase C, the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA; 1 x 10(-7) M). Myotubes exhibited a spontaneous channel activity when the TPA-induced dedifferentiative processes developed. This consisted in the activation of inward current channels (approximately 35 pS conductance; approximately 6 ms open time). These spontaneously active channels were insensitive to alpha-bungarotoxin, curare, atropine and tetrodotoxin and were not inhibited by the withdrawal of TPA. It is suggested that a prolonged stimulation of the protein kinase C causes a irreversible deregulation of the membrane channel function during cell dedifferentiation.

Age-dependent changes of relaxation and its load sensitivity in rat cardiac muscle.

The relaxation phase and its load dependence were studied in papillary muscles isolated from the left ventricle of rats of the following ages: 20 days, 2, 8, 18, and 24 months. The myofibrillar ATPase activity and the force-velocity relation were determined in each age group in order to characterize the kinetic properties of the contractile material. Both shortening velocity and myofibrillar ATPase activity showed a progressive reduction with maturation and aging. This observation suggested an age-dependent decrease in cross bridge formation rate. The relaxation phase was characterized by its duration and the maximum rate of tension decline in isometric conditions, and by the speed of relengthening in isotonic conditions. Relaxation became faster and of shorter duration with maturation from 20 days to 2 months and then became slower and of longer duration with further maturation and aging. The sensitivity of relaxation to changes in length or load was evaluated by measuring how much earlier tension declined in the presence of a given length change. An increase in load sensitivity of relaxation was observed during maturation from 20 days to 8 months. This increase was followed by a reduction during aging from 8 to 24 months. Such a biphasic trend of the age-related changes in load sensitivity of relaxation could result from the interplay between the progressive decrease in cross bridge formation rate and a reduction in activation decay rate. The latter was suggested by the prolongation of the relaxation phase and by the maintenance of developed tension during aging.