Genetic factors underlying insomnia and ovarian insufficiency.

Premature ovarian insufficiency (POI) is characterized by a loss of regular hormone production and egg release in women below the age of 40 years, which often leads to infertility, vaginal dryness and dysfunctional sleep. Acknowledging the common co-occurrence of insomnia and POI, we tested the overlap between POI and insomnia-associated genes, which were implicated in previous large-scale populational genetics efforts. Among the 27 overlapping genes, three pathways were found as enriched: DNA replication, homologous recombination and Fanconi anemia. We then describe biological mechanisms, which link these pathways to a dysfunctional regulation and response to oxidative stress. We propose that oxidative stress may correspond to one of the convergent cellular processes between ovarian malfunction and insomnia pathogenic etiology. This overlap might also be driven by cortisol release associated with dysregulated DNA repair mechanisms. Benefiting from the enormous advances in populational genetics studies, this study provides a novel outlook on the relationship between insomnia and POI. The shared genetic factors and critical biological nodes between these two comorbidities may lead to identification of putative pharmacological and therapeutical targets, which can leverage novel approaches to treat or alleviate their symptoms.

Adult skin acute stress responses to short-term environmental and internal aggression from exposome factors.

Exposome factors that lead to stressed skin can be defined as any disturbance to homeostasis from environmental (meteorological factors, solar radiation, pollution or tobacco smoke) and/or internal exposure (unhealthy diet, hormonal variations, lack of sleep, psychosocial stress). The clinical and biological impact of chronic exposome effects on skin functions has been extensively reviewed, whereas there is a paucity of information on the impact of short-term acute exposure. Acute stress, which would typically last minutes to hours (and generally no more than a week), provokes a transient but robust neuroendocrine-immune and tissue remodelling response in the skin and can alter the skin barrier. Firstly, we provide an overview of the biological effects of various acute stressors on six key skin functions, namely the skin physical barrier, pigmentation, defences (antioxidant, immune cell-mediated, microbial and microbiome maintenance), structure (extracellular matrix and appendages), neuroendocrine and thermoregulation functions. Secondly, we describe the biological and clinical effects on adult skin from individual exposome factors that elicit an acute stress response and their consequences in skin health maintenance. Clinical manifestations of acutely stressed skin may include dry skin that might accentuate fine lines, oily skin, sensitive skin, pruritus, erythema, pale skin, sweating, oedema and flares of inflammatory skin conditions such as acne, rosacea, atopic dermatitis, pigmentation disorders and skin superinfection such as viral reactivation. Acute stresses can also induce scalp sensitivity, telogen effluvium and worsen alopecia.

Sleep bruxism and its associations with insomnia and OSA in the general population of Sao Paulo.

Sleep bruxism (SB) is characterized by recurrent masticatory muscle activity during sleep with occasional tooth grinding. SB can be concomitant with sleep apnea although its association with insomnia is understudied. STUDY OBJECTIVE: Assess the strength of the associations between SB, insomnia and sleep apnea in a general population. METHODS: Data from the 2007 EPISONO general population study (n = 1042; Sao Paulo, Brazil) were reused for the present analyses. The data was collected from polysomnography (PSG) and from a questionnaire. SB could only be assessed as "possible" with self-report questionnaires, but as "definitive" with both self-reports and PSG. Logistic regression and decision tree analyses were performed. RESULTS: Logistic regression analyses revealed that being male, overweight, obese, having an apnea/hypopnea index (AHI) above 30 and insomnia syndrome are among risk factors for SB (prevalence ratio (PR): 1.5-3.3). A high AHI and insomnia syndrome had similar PRs, 2.7 and 2.8, respectively. Decision tree analysis showed that insomnia syndrome contributed to the predictive accuracy of SB self-report (88%). A similar estimate (91%) was observed with SB PSG data. Correspondence analysis illustrated three age profiles in participants: (1) good sleepers aged 20-35 years, (2) females aged 35-50 years with SB and concomitant insomnia syndrome, and (3) participants aged ≥ 50 years with obesity and sleep apnea. CONCLUSIONS: Insomnia is likely a condition associated with SB, especially in middle-age females, while sleep apnea seems age and gender dependent. Such overlap may influence the treatment decision to achieve best outcomes. CLINICAL TRIAL REGISTRATION: EPISONO study; Clinical trials.gov ID # NCT00596713.

Clinical and biological impact of the exposome on the skin.

The skin exposome is defined as the totality of environmental exposures over the life course that can induce or modify various skin conditions. Here, we review the impact on the skin of solar exposure, air pollution, hormones, nutrition and psychological factors. Photoageing, photocarcinogenesis and pigmentary changes are well-established consequences of chronic exposure of the skin to solar radiation. Exposure to traffic-related air pollution contributes to skin ageing. Particulate matter and nitrogen dioxide cause skin pigmentation/lentigines, while ozone causes wrinkles and has an impact on atopic eczema. Human skin is a major target of hormones, and they exhibit a wide range of biological activities on the skin. Hormones decline with advancing age influencing skin ageing. Nutrition has an impact on numerous biochemical processes, including oxidation, inflammation and glycation, which may result in clinical effects, including modification of the course of skin ageing and photoageing. Stress and lack of sleep are known to contribute to a pro-inflammatory state, which, in turn, affects the integrity of extracellular matrix proteins, in particular collagen. Hormone dysregulation, malnutrition and stress may contribute to inflammatory skin disorders, such as atopic dermatitis, psoriasis, acne and rosacea.

Sleep disturbance and atopic dermatitis: A bidirectional relationship?

Atopic dermatitis (AD) is one of the most common pediatric dermatologic disorders and is associated with an increased risk of recurrent bacterial and viral cutaneous infections, such as impetigo, the most common bacterial infection in children. AD may impair patient quality of life in a number of ways, one of which is its impact on sleep. The way that the condition affects sleep has not yet been fully elucidated; it is clear that the symptoms of the disease such as pruritus and scratching can affect sleep but other factors, such as changes in the immunological system related to the disease can also have an effect. We argue that this relationship may be bi-directional, with changes to the skin barrier (barrier dysfunction, alterations in its microbiome and oxidative stress) and immunological function caused by the condition impairing sleep and leading to imbalanced inflammatory pathways that exacerbate AD and other associated conditions such as impetigo. We highlight the need for further studies to investigate this correlation between AD and sleep to make the role of this relationship clearer.

Protective effects of Hydrocotyle umbellata var. bonariensis Lam. (Araliaceae) on memory in sleep-impaired female mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Hydrocotyle umbellata var.bonariensis Lam. (Hb), popularly known in Brazil as acariçoba and outside Brazil Hb by a number of names including marsh-pennywort, and many-flower, has traditionally been used in Ayurvedic medicine in the retardation of aging (Rasayana effect). AIM OF THE STUDY: The present study evaluated the effect of Hb treatment before and during paradoxical sleep deprivation (PSD) and sleep restriction (SR) on learning, memory, and acetylcholinesterase (AChE) brain activity. MATERIAL AND METHODS: Adult Swiss nulliparous female mice were randomly distributed among the experimental groups. The treated groups received the aqueous solution of Hb leaves orally at concentrations of 500 and 1.000 mg/kg. PSD and SR were induced by the multiple platform method, in which the animals remained for 3-days in PSD or 15-days in SR for 22 h per day. The collection of the vaginal epithelium occurred daily to determine the estrous cycle. Body mass gain was determined. The animals were submitted to the passive avoidance test and were then euthanized for the collection of brain tissue and the determination of cerebral cholinesterase activity. RESULTS: The aqueous solution of Hb was associated with a significant reduction in cholinesterase activity at both doses in the SR model, and at the dose of 1.000 mg/kg in the PSD model. Regarding the learning and memory test, the PSD group treated with 1.000 mg/kg presented significant improvement, whereas in the SR experiment none of the treated-groups showed any improvement in learning and memory. In the analysis of SR/PSD interference and/or Hb treatment on the estrous cycle, it was possible to observe that the treatment acted as a protector in the SR group, maintaining a normal cycle. CONCLUSIONS: The analyses showed that Hb was safe to use during periods of SR or PSD, acting as an adaptogen for these situations, in addition to being able to reduce cholinesterase activity, which suggests its neuroprotective action. In relation to the estrous cycle, Hb can act as a protector in SR situations.

The interaction between erectile dysfunction complaints and depression in men: a cross-sectional study about sleep, hormones and quality of life.

Depression (DEP) is one of the main disabling diseases and is considered a contributor factor for erectile dysfunction (ED). Both of these conditions may be associated with hormonal changes and sleep disturbances. We aimed to evaluate the interaction between ED complaints and depression symptoms on sleep parameters, hormone levels and quality of life in men. This was a cross-sectional study of 468 men aged 20-80 years. The participants were classified according to the presence of ED and/or DEP in groups of healthy individuals, ED, DEP and DEP with ED (DEP-ED). All participants completed questionnaires about sleep, clinical history and quality of life, and underwent polysomnography with blood collection the following morning. ED participants showed higher frequency of insomnia symptoms (65.5%), whereas DEP group had more complaints of difficulty in falling asleep and early morning awakening. In the polysomnography, all groups showed similar parameters. No differences were found in cortisol and total testosterone levels; however, free testosterone levels and the physiological domain of quality of life were lower in DEP-ED group. ED and DEP, as independent factors, negatively affected subjective sleep parameters. The interaction between these factors led to a low quality of life and was related to a decrease in free testosterone levels.

Musculoskeletal pain and the reproductive life stage in women: is there a relationship?

Objectives To investigate the association between reproductive life stage, pain perception and musculoskeletal pain complaint in a representative sample of women from São Paulo, Brazil. Methods A population-based survey was carried out with 574 women who were classified as being in the premenopausal or postmenopausal stage. They answered questions about pain perception and musculoskeletal pain. Follicle stimulating hormone was collected to confirm menopausal condition along with clinical evaluation. Results In the whole sample, we found a prevalence of 56% for pain perception and 20.2% for complaints of musculoskeletal pain. Regarding the topography of musculoskeletal pain, the distributions were similar among the premenopausal and postmenopausal groups. No significant association was found between reproductive life stage and pain perception, as 58.1% of the premenopausal group and 52.0% of the postmenopausal group reported pain. Similarly, there was no significant association between menopausal stage and musculoskeletal pain, as 19.5% and 21.6% of the premenopausal and postmenopausal women, respectively, complained of musculoskeletal pain. There was no significant association of postmenopausal stage (early or late) with pain perception or musculoskeletal pain. The use of analgesics was significantly higher in postmenopausal compared to premenopausal women (p < 0.001). Conclusion A high prevalence of pain was found in women from the city of São Paulo. However, neither the presence of musculoskeletal pain nor pain perception were associated with the reproductive life stage, showing that both parameters was independent from the menopausal status in the studied women.

Liquid-core nanocellulose-shell capsules with tunable oxygen permeability.

Encapsulation of oxygen sensitive components is important in several areas, including those in the food and pharmaceutical sectors, in order to improve shelf-life (oxidation resistance). Neat nanocellulose films demonstrate outstanding oxygen barrier properties, and thus nanocellulose-based capsules are interesting from the perspective of enhanced protection from oxygen. Herein, two types of nanocellulose-based capsules with liquid hexadecane cores were successfully prepared; a primary nanocellulose polyurea-urethane capsule (diameter: 1.66 µm) and a bigger aggregate capsule (diameter: 8.3 µm) containing several primary capsules in a nanocellulose matrix. To quantify oxygen permeation through the capsule walls, an oxygen-sensitive spin probe was dissolved within the liquid hexadecane core, allowing non-invasive measurements (spin-probe oximetry, electron spin resonance, ESR) of the oxygen concentration within the core. It was observed that the oxygen uptake rate was significantly reduced for both capsule types compared to a neat hexadecane solution containing the spin-probe, i.e. the slope of the non-steady state part of the ESR-curve was approximately one-third and one-ninth for the primary nanocellulose capsule and aggregated capsule, respectively, compared to that for the hexadecane sample. The transport of oxygen was modeled mathematically and by fitting to the experimental data, the oxygen diffusion coefficients of the capsule wall was determined. These values were, however, lower than expected and one plausible reason for this was that the ESR-technique underestimate the true oxygen uptake rate in the present systems at non-steady conditions, when the overall diffusion of oxygen was very slow.

Acupuncture to Treat Sleep Disorders in Postmenopausal Women: A Systematic Review.

Sleep disorders are commonly observed among postmenopausal women, with negative effects on their quality of life. The search for complementary therapies for sleep disorders during postmenopausal period is of high importance, and acupuncture stands out as an appropriate possibility. The present review intended to systematically evaluate the available literature, compiling studies that have employed acupuncture as treatment to sleep disorders in postmenopausal women. A bibliographic search was performed in PubMed/Medline and Scopus. Articles which had acupuncture as intervention, sleep related measurements as outcomes, and postmenopausal women as target population were included and evaluated according to the Cochrane risk of bias tool and to the STRICTA guidelines. Out of 89 search results, 12 articles composed our final sample. A high heterogeneity was observed among these articles, which prevented us from performing a meta-analysis. Selected articles did not present high risk of bias and had a satisfactory compliance rate with STRICTA guidelines. In general, these studies presented improvements in sleep-related variables. Despite the overall positive effects, acupuncture still cannot be stated as a reliable treatment for sleep-related complaints, not due to inefficacy, but rather limited evidence. Nevertheless, results are promising and new comprehensive and controlled studies in the field are encouraged.

Musicians and Dystonia: Is Sleep Part of the Problem?

We would like to congratulate Lee and Altenmüller for their recent study showing important findings about the characterization of a task-specific dystonia in a young professional percussionist. The authors presented in an elegant way the EMG investigation and treatment approach and the possible differential diagnoses, raising an important question about the need for physicians' awareness of this condition when considering musicians' health. We would like to add a new point of view in order to contribute with this discussion and provide critical thinking for a multidisciplinary approach to this type of dystonia, which may affect many individuals and result in severe compromise of musical technical performance. One factor that could also be potentially associated with the percussion-related dystonia is sleep.

Prevalence and predictors of severe hypoglycemia in Danish children and adolescents with diabetes.

OBJECTIVE: To investigate the prevalence of severe hypoglycemia in Danish children and adolescents with type 1 diabetes and to pinpoint predictors of this acute complication in children on modern treatment modalities. RESEARCH DESIGN AND METHODS: The study is based on data from DanDiabKids, a national diabetes register for children and adolescents. The register contains data on patients with type 1 diabetes with an ascertainment rate of 99%. Data from 3320 patients aged 0-18 yr was included in the study period from 1998 to 2009 and analyzed using a negative binomial model. RESULTS: One thousand nine hundred and ninety-nine episodes of severe hypoglycemia in 867 patients were registered conferring an overall incidence of severe hypoglycemia of 15.1 [95% confident interval (CI): 13.8; 16.4] per 100 patient years. This remained unchanged during the study period. Duration of diabetes, age and treatment in centers managing less than 100 patients significantly increased the risk of severe hypoglycemia (p < 0.001). Patients on insulin pump therapy had a 42% reduced risk of severe hypoglycemia compared with pen treated patients (p = 0.01). Patients treated with five or more daily insulin injections had a 31% (95% CI: 17; 49) reduced risk of severe hypoglycemia compared to patients on fewer daily injections (p = 0.015). CONCLUSIONS: Despite improvements in metabolic control over a decade the prevalence of severe hypoglycemic events remained unchanged. More intensive treatments such as insulin pump therapy and multiple daily injections on a national level seems to be a protective factor for developing severe hypoglycemia up to 2009.

The role of progesterone in memory: an overview of three decades.

Memory comprises acquisition, consolidation and retrieval of information. Many substances can influence these different phases. It is well demonstrated that sex hormones, mainly estrogen, impact cognitive function. More recently, progesterone has also been documented as playing an important role in cognition, since it influences brain regions involved in memory. Currently, many women are under hormone treatment, which contain progesterone to decrease the risk of development of endometrial cancer. This affords the opportunity to study the real effects of this hormonal replacement on cognition. There are many contradictory results regarding the role of progesterone in memory. Therefore, the aim of this review was to synthesize these studies using the new perspective of the influence of hormone replacement on cognition in women.