Music therapy for supporting informal carers of adults with life-threatening illness pre- and post-bereavement; a mixed-methods systematic review.

BACKGROUND: Music therapy interventions with informal carers of individuals with life-threatening illness at pre- and post-bereavement is an increasingly important clinical area. This systematic review is the first to synthesise and critically evaluate the international evidence associated with music therapy with adult informal carers pre- and post-bereavement. Specifically, the objectives were: i) to describe the characteristics and effectiveness of music therapy interventions which aim to improve health-related outcomes for adult informal carers of adults with life-threatening illness (pre- and post-bereavement), and ii) to describe the experience of music therapy for adult informal carers of adults with life-threatening illness (pre- and post-bereavement). METHODS: Eligibility: adult informal carers of adults at end of life or bereaved; music therapy interventions for improving health-related outcomes; qualitative; mixed-method; and quantitative studies including comparators of any other intervention; published in English from 1998 onwards. Six databases were searched up to July 2022. A JBI mixed-methods systematic review approach was followed throughout, including quality appraisal, data extraction and a convergent segregated approach to synthesis and integration. RESULTS: A total of 34 studies were included, published between 2003 and 2022. Most were conducted in North America (n = 13), Australia (n = 10), or Europe (n = 8). No studies were conducted in low- and middle-income countries or in the UK. The majority were qualitative (n = 17), followed by quasi-experimental (n = 8), mixed-methods (n = 7) and two RCTs. The majority focused on carers of individuals with dementia (n = 21) or advanced cancer (n = 7). Seventeen studies were purely quantitative or included a quantitative component. During meta-synthesis, findings were aligned to core outcomes for evaluating bereavement interventions in palliative care and previously identified risk factors for complicated grief. Commonly targeted outcomes in quantitative studies included quality of life and mental wellbeing, showing equivocal effectiveness of music therapy with significant and non-significant results. Twenty-two studies either purely qualitative or with a qualitative component underwent meta synthesis and suggested a diverse range of improved pre- and post-bereavement outcomes for informal carers across all core outcomes, and across all risk and protective factors, including psychological, spiritual, emotional, and social outcomes. CONCLUSIONS: Qualitative studies provide moderate to strong evidence for improved health-related outcomes for adult informal carers of adults with life-threatening illness pre-bereavement. Limited studies including those bereaved negates conclusions for the bereavement phase. Comparisons and explanations for effectiveness across quantitative and qualitative studies are equivocal, with a high risk of bias and small samples in the limited number of quantitative studies, demonstrating a need for high-quality RCTs. SYSTEMATIC REVIEW PRE-REGISTRATION: PROSPERO [CRD42021244859].

Immunolocalization of transforming growth factor-beta 1 and transforming growth factor-beta 2 in the mouse ovary during gonadotrophin-induced follicular maturation.

An immunohistochemical approach was utilized to evaluate the cellular distribution of transforming growth factor-beta 1 (TGF beta 1) and transforming growth factor beta 2 (TGF beta 2) at different stages of follicle development in the prepubertal mouse ovary under the following conditions: (i) after pregnant mare's serum gonadotrophin (PMSG) treatment; (ii) after PMSG and human chorionic gonadotrophin (HCG) treatment; (iii) after PMSG and HCG treatment plus mating. In the immature ovary, TGF beta 1 and TGF beta 2 immunoreactivities are localized in theca and granulosa cells and in oocytes. After PMSG treatment, TGF beta 1 and TGF beta 2 immunoreactivities are localized in granulosa cells; in addition, TGF beta 2 staining is noted in the matrix surrounding antral cells. Staining for both TGR beta 1 and TGF beta 2 drops in the theca but persists in the oocyte. PMSG plus HCG treatment results in a significant increase in TGF beta 1 and TGF beta 2 immunoreactivity in the theca and in the maintenance of TGF beta 1 staining in both basal granulosa cells and cumulus cells whereas TGF beta 2 immunoreactivity is essentially localized in the matrix surrounding cumulus cells. Staining for TGF beta 1 and TGF beta 2 persists in the oocyte. Following PMSG plus HCG treatment and mating, TGF beta 1 immunoreactivity is localized in the luteal cells of corpora lutea and TGF beta 2 shows a similar localization pattern. This study provides evidence that TGF beta 1 and TGF beta 2 peptides are expressed in specific cell types during induced follicular maturation in the mouse ovary.

Transforming growth factor beta 1 inhibits gonadotropin action in cultured porcine Sertoli cells.

In the present study, we have tested the effects of transforming growth factor beta 1 (TGF beta 1) on FSH action toward aromatase activity and lactate production in cultured Sertoli cells isolated from immature porcine testes. Whereas treatment of Sertoli cells with FSH resulted in a dose-dependent increase (about 7-fold) in aromatase activity (conversion of testosterone into estradiol) (ED50 = 80 ng/ml FSH), the addition of TGF beta 1 reduced this gonadotropin action. The inhibitory effect of TGF beta 1 on FSH aromatase activity was dose dependent (ED50 = 0.1 ng/ml, 4 pM TGF beta 1) with a maximal decrease (about 40%) observed after a long term (48-h) treatment. TGF beta 1 exerted its inhibitory effect on FSH action at the level(s) of cAMP accumulation, exerting no apparent effect on the gonadotropin receptor or at a site(s) related to cAMP action. TGF beta 1 (2 ng/ml) significantly (P less than 0.002) reduced (52% decrease) FSH-stimulated cAMP levels in cultured porcine Sertoli cells. However, such an inhibitory effect of the growth factor was no longer observed when stimulation of cAMP accumulation with FSH occurred in the presence of methyl isobutyl xanthine (0.5 mM), an inhibitor of cAMP-phosphodiesterase activity. This observation suggests that TGF beta 1 decreased cAMP levels by increasing catabolism of the cyclic nucleotide through an enhancement of cAMP-phosphodiesterase activity. The inhibitory effect of TGF beta 1 was not limited to the action of FSH on aromatase activity but also extended to the gonadotropin action (mediated by cAMP) on lactate production. As for the inhibitory effect of TGF beta 1 on FSH-induced aromatase activity, the inhibitory effect of the growth factor on FSH-stimulated lactate production was dose and time dependent with a maximal decrease (about 30%) observed in the picomolar range (1 ng/ml, 40 pM) after 48 h treatment with TGF beta 1. In conclusion, the present study demonstrates that TGF beta 1 attenuates FSH action on Sertoli cell activity and that such inhibitory action is potentially exerted through a decrease in cAMP levels. Because of the local production of TGF beta 1, it is suggested that the effects of the growth factor reported here might be exerted in the context of the testicular paracrine mechanisms.

[Interaction between gonadotropins and "Transforming Growth Factor Beta" (TGF Beta) in testicular function control]. / Interactions entre les gonadotrphines et le "Transforming Growth Factor beta " (TGF beta) dans le contröle des fonctions testiculaires.

Testicular function is regulated not only by circulating hormones, among which the gonadotrophins play the main role, but also by local factors originating in multiple and complex interactions among cells. In this review, the example of gonadotrophins (LH and FSH) and Transforming Growth Factor beta (TGF beta) was chosen to illustrate the role of interactions between circulating hormones and gonadal growth factors in testicular function control; TGF beta-like activity has been found in the male gonad and we have used a model of cultured purified testicular cells to show that the action of TGF beta on testicular function mainly involves antagonism of the effect of gonadotrophins. Conversely, TGF beta promotes differentiated Leydig and Sertoli cell function. The example of interactions between TGF beta and gonadotrophins reported here shows that locally produced growth factors can regulate the response of testicular cells to gonadotrophins, a finding that extends our concept of reproductive endocrinology to cell-cell interactions.