The Role of Music Therapy with Infants with Perinatal Brain Injury.

Perinatal brain injury occurs in 5.14/1000 live births in England. A significant proportion of these injuries result from hypoxic ischaemic encephalopathy (HIE) in term infants and intracranial haemorrhage (IVH) or periventricular leukomalacia (PVL) in preterm infants. Standardised care necessitates minimal handling from parents and professionals to reduce the progression of injury. This can potentially increase parental stress through the physical inability to bond with their baby. Recent research highlights the ability of music therapy (MT) to empower parental bonding without handling, through sharing culturally informed personal music with their infant. This review therefore aimed to systematically evaluate the use of MT with infants diagnosed with perinatal brain injury in a neonatal intensive care unit (NICU). Search terms were combined into three categories (audio stimulation (MT), population (neonates) and condition (brain injury), and eight electronic databases were used to identify relevant studies following PRISMA guidelines. Eleven studies using music or vocal stimulation with infants diagnosed with perinatal brain injury were identified and quality assessed using Cochrane ROB2, the ROBINSI Tool and the Newcastle Ottawa Scale. Studies used either voice as live (n = 6) or pre-recorded (n = 3) interventions or pre-recorded instrumental music (n = 2). Studies had two primary areas of focus: developmental outcomes and physiological effects. Results suggested the use of music interventions led to a reduction of infants' pain scores during procedures and cardiorespiratory events, improved feeding ability (increase oral feeding rate, volume intake and feeds per day) and resulted in larger amygdala volumes than control groups. Additionally, MT intervention on the unit supported long-term hospitalised infants in the acquisition of developmental milestones. Vocal soothing was perceived to be an accessible intervention for parents. However, infants with PVL showed signs of stress in complex interventions, which also potentially resulted in an increase in maternal anxiety in one study. MT with infants diagnosed with perinatal brain injury can have positive effects on infants' behavioural and neurological parameters and support parental involvement in their infants' developmental care. Further feasibility studies are required using MT to determine appropriate outcome measures for infants and the support required for parents to allow future comparison in large-scale randomised control trials.

Co-administering Melatonin With an Estradiol-Progesterone Menopausal Hormone Therapy Represses Mammary Cancer Development in a Mouse Model of HER2-Positive Breast Cancer.

Melatonin has numerous anti-cancer properties reported to influence cancer initiation, promotion, and metastasis. With the need for effective hormone therapies (HT) to treat menopausal symptoms without increasing breast cancer risk, co-administration of nocturnal melatonin with a natural, low-dose HT was evaluated in mice that develop primary and metastatic mammary cancer. Individually, melatonin (MEL) and estradiol-progesterone therapy (EPT) did not significantly affect mammary cancer development through age 14 months, but, when combined, the melatonin-estradiol-progesterone therapy (MEPT) significantly repressed tumor formation. This repression was due to effects on tumor incidence, but not latency. These results demonstrate that melatonin and the HT cooperate to decrease the mammary cancer risk. Melatonin and EPT also cooperate to alter the balance of the progesterone receptor (PR) isoforms by significantly increasing PRA protein expression only in MEPT mammary glands. Melatonin significantly suppressed amphiregulin transcripts in MEL and MEPT mammary glands, suggesting that amphiregulin together with the higher PRA:PRB balance and other factors may contribute to reducing cancer development in MEPT mice. Melatonin supplementation influenced mammary morphology by increasing tertiary branching in the mouse mammary glands and differentiation in human mammary epithelial cell cultures. Uterine weight in the luteal phase was elevated after long-term exposure to EPT, but not to MEPT, indicating that melatonin supplementation may reduce estrogen-induced uterine stimulation. Melatonin supplementation significantly decreased the incidence of grossly-detected lung metastases in MEL mice, suggesting that melatonin delays the formation of metastatic lesions and/or decreases aggressiveness in this model of HER2+ breast cancer. Mammary tumor development was similar in EPT and MEPT mice until age 8.6 months, but after 8.6 months, only MEPT continued to suppress cancer development. These data suggest that melatonin supplementation has a negligible effect in young MEPT mice, but is required in older mice to inhibit tumor formation. Since melatonin binding was significantly decreased in older mammary glands, irrespective of treatment, melatonin supplementation may overcome reduced melatonin responsiveness in the aged MEPT mice. Since melatonin levels are known to decline near menopause, nocturnal melatonin supplementation may also be needed in aging women to cooperate with HT to decrease breast cancer risk.

Effects on bone by the light/dark cycle and chronic treatment with melatonin and/or hormone replacement therapy in intact female mice.

In this study, the effects of the light/dark cycle, hormone replacement therapy (HRT), and nocturnal melatonin supplementation on osteogenic markers and serum melatonin levels were examined in a blind mouse model (MMTV-Neu transgenic mice). Melatonin levels in this mouse strain (FVB/N) with retinal degeneration (rd-/-) fluctuate in a diurnal manner, suggesting that these mice, although blind, still perceive light. Real-time RT-PCR analyses demonstrated that Runx2, Bmp2, Bmp6, Bglap, and Per2 mRNA levels coincide with melatonin levels. The effect of chronic HRT (0.5 mg 17ß-estradiol + 50 mg progesterone in 1800 kcal of diet) alone and in combination with melatonin (15 mg/L drinking water) on bone quality and density was also assessed by histomorphometry and microcomputed tomography, respectively. Bone density was significantly increased (P < 0.05) after 1 yr of treatment with the individual therapies, HRT (22% increase) and nocturnal melatonin (20% increase) compared to control. Hormone replacement therapy alone also increased surface bone, decreased trabecular space, and decreased the number of osteoclasts without affecting osteoblast numbers compared to the control group (P < 0.05). Chronic HRT + melatonin therapy did not significantly increase bone density, even though this combination significantly increased Bglap mRNA levels. These data suggest that the endogenous melatonin rhythm modulates markers important to bone physiology. Hormone replacement therapy with or without nocturnal melatonin in cycling mice produces unique effects on bone markers and bone density. The effects of these therapies alone and combined may improve bone health in women in perimenopause and with low nocturnal melatonin levels from too little sleep, too much light, or age.

Nutrient intake in community-dwelling adolescent girls with anorexia nervosa and in healthy adolescents.

BACKGROUND: Adolescence is a common time for the onset of anorexia nervosa (AN), a condition associated with long-term medical and hormonal consequences. OBJECTIVE: The objective was to compare the nutrient intakes of community-dwelling girls with AN with those of healthy adolescents and to describe the associations between specific nutrient intakes and nutritionally dependent hormones. DESIGN: Nutrient intakes in 39 community-dwelling girls with AN and 39 healthy adolescents aged 12.1-18.7 y were determined by using 4-d food records. Fasting adiponectin, leptin, ghrelin, insulin, and insulin-like growth factor I (IGF-I) concentrations were measured. Indirect calorimetry was used to assess respiratory quotient and resting energy expenditure. RESULTS: In contrast with the control group, the AN group consumed fewer calories from fats (P < 0.0001) and more from carbohydrates (P = 0.0009) and proteins (P < 0.0001). Intake of individual fat components was lower and of dietary fiber higher in the AN group. No significant between-group differences were observed in dietary intakes of calcium, zinc, and iron; however, total intake was greater in the AN group because of greater supplement use (P = 0.006, 0.02, and 0.01, respectively). The AN group had greater intakes of vitamins A, D, and K and of most of the B vitamins, and significantly more girls with AN met the Dietary Reference Intake for calcium (P = 0.01) and vitamin D (P = 0.02) from supplement use. Fat intake predicted ghrelin, insulin, and IGF-I concentrations; carbohydrate intake predicted adiponectin. Resting energy expenditure was lower (P < 0.0001) and leisure activity levels higher in the AN group. CONCLUSIONS: Despite outpatient follow-up, community-dwelling girls with AN continue to have lower fat and higher fiber intakes than do healthy adolescents, which results in lower calorie intakes. Nutritionally related hormones are associated with specific nutrient intakes.