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PurposeThe purpose of this paper is to explore the mediating effect of the work–family conflict in the relation between ethical leadership and job satisfaction.Design/methodology/approachA questionnaire was answered by 234 nursing professionals working in Portuguese public health institutions.FindingsRegression analyses indicate that there is a positive relationship between ethical leadership and satisfaction and a negative relationship between ethical leadership and the nurse's work–family conflict. Furthermore, it was revealed that the work–family conflict mediated (partially) the relationship between ethical leadership and job satisfaction.Research limitations/implicationsEthical leadership was measured by assessing the nurses' perceptions of their leaders' character. The cross-sectional data limited the possibility of establishing the causality of the study variables, where the generalization of results was not possible due to the fact that data were obtained in public health institutions alone.Practical implicationsConsidering that ethics precede good relations between the manager and collaborator, it is recommended that organizations develop ethical training for their leaders, more specifically in the case of head nurses.Originality/valueThe added value of this empirical study lies in the mediated role of the work–family conflict in the analysis of the relationship between ethical leadership and job satisfaction.

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway due to the loss of upper airway muscle tone during sleep. OSA is highly prevalent, especially in obesity. There is no pharmacotherapy for OSA. Previous studies have demonstrated the role of leptin, an adipose-tissue-produced hormone, as a potent respiratory stimulant. Leptin signaling via a long functional isoform of leptin receptor, LEPRb, in the nucleus of the solitary tract (NTS), has been implicated in control of breathing. We hypothesized that leptin acts on LEPRb positive neurons in the NTS to increase ventilation and maintain upper airway patency during sleep in obese mice. We expressed designer receptors exclusively activated by designer drugs (DREADD) selectively in the LEPRb positive neurons of the NTS of Leprb-Cre-GFP mice with diet-induced obesity (DIO) and examined the effect of DREADD ligand, J60, on tongue muscle activity and breathing during sleep. J60 was a potent activator of LEPRb positive NTS neurons, but did not stimulate breathing or upper airway muscles during NREM and REM sleep. We conclude that, in DIO mice, the stimulating effects of leptin on breathing during sleep are independent of LEPRb signaling in the NTS.

Rationale: North America is currently facing an opioid epidemics. Over 130 Americans die every day from an opioid overdose and the COVID-19 pandemic has increased opioid usage and opioid-related deaths. Respiratory depression is the main cause of morbidity and mortality from opioids. We have previously shown that leptin acts as respiratory stimulant and prevents opioid-induced respiratory depression and upper airway obstruction without reducing analgesia. In this study, we aimed to examine if intranasal (IN) administration of leptin effectively delivers leptin to the brain and prevents opioid-related deaths. Methods: To determine leptin delivery to the brain male C57BL/6J mice, were treated with IN leptin at 1.2 mg/kg in 1% BSA (n=5) or 1% BSA (n=5) and sacrificed 20 min later. Brains were harvested, the olfactory bulbs, medullas and hypotalami were isolated, quick frozen and stored at-80°C. For leptin level measurements, brain tissue was homogenized, protease inhibitors and protein concentrations were determined and ELISA was performed. To determine the survival probability, male C57BL/6J mice, 12 weeks of age, received IN leptin (n=26) or vehicle (n=25) at 1.2 mg/kg and 30 minutes later received a bolus of intraperitoneal (IP) morphine at 400mg/kg. Mice were video monitored for 24 hours and survival time after morphine injection was recorded Results: IN leptin significantly increased leptin levels in the olfactory bulb (from 0 ng/mL to 7.53 ng/mL, p = 0.004) and medulla (from 0.008 ng/mL to 0.107 ng/mL) and presented a trend in the hypothalamus (from 0.018 ng/mL to 0.291 ng/mL, p = 0.1). Mice that received IN leptin had a higher survival rate when compared to mice that received vehicle (69% vs 92%, p = 0.044, Figure). Conclusion: We demonstrated that the intranasal route is effective for the delivery of leptin to the brain and that leptin reduced opioid-induced mortality. (Table Presented).

Study Objectives Obesity leads to obstructive sleep apnea (OSA), which is recurrent upper airway obstruction during sleep, and obesity hypoventilation syndrome (OHS), hypoventilation during sleep resulting in daytime hypercapnia. Impaired leptin signaling in the brain was implicated in both conditions, but mechanisms are unknown. We have previously shown that leptin stimulates breathing and treats OSA and OHS in leptin-deficient ob/ob mice and leptin-resistant diet-induced obese mice and that leptin’s respiratory effects may occur in the dorsomedial hypothalamus (DMH). We hypothesized that leptin receptor LepRb-deficient db/db mice have obesity hypoventilation and that restoration of leptin signaling in the DMH will increase ventilation during sleep in these animals. Methods We measured arterial blood gas in unanesthetized awake db/db mice. We subsequently infected these animals with Ad-LepRb or control Ad-mCherry virus into the DMH and measured ventilation during sleep as well as CO2 production after intracerebroventricular (ICV) infusions of phosphate-buffered saline or leptin. Results Awake db/db mice had elevated CO2 levels in the arterial blood. Ad-LepRb infection resulted in LepRb expression in the DMH neurons in a similar fashion to wildtype mice. In LepRb-DMH db/db mice, ICV leptin shortened REM sleep and increased inspiratory flow, tidal volume, and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2 production. Leptin had no effect on upper airway obstruction in these animals. Conclusion Leptin stimulates breathing and treats obesity hypoventilation acting on LepRb-positive neurons in the DMH.

Obesity can lead to recurrent upper airway obstruction (obstructive sleep apnea, OSA) during sleep as well as alveolar hypoventilation. We have previously shown that leptin stimulates breathing and treats OSA in leptin-deficientob/obmice and leptin-resistant diet-induced obese mice. Our previous data also suggest that leptin’s respiratory effects may occur in the dorsomedial hypothalamus (DMH). We selectively expressed leptin receptorLepRbin the DMH neurons of obeseLepRb-deficientdb/dbmice (LepRb-DMH mice), which hypoventilate at baseline, and showed that intracerebroventricular injection of leptin in these animals increased inspiratory flow, tidal volume and minute ventilation during NREM sleep without any effect on the quality of NREM sleep or CO2production. Leptin had no effect on upper airway obstruction inLepRb-DMHanimals. We conclude that leptin stimulates breathing and treats obesity related hypoventilation acting on LepRb-positive neurons in the DMH.

Respiratory depression is the main cause of morbidity and mortality associated with opioids. Obesity increases opioid-related mortality, which is mostly related to comorbid obstructive sleep apnea. Naloxone, a μ-opioid receptor blocker, is an effective antidote, but it reverses analgesia. Like humans with obesity, mice with diet-induced obesity hypoventilate during sleep and develop obstructive sleep apnea, which can be treated with intranasal leptin. We hypothesized that intranasal leptin reverses opioid-induced sleep-disordered breathing in obese mice without decreasing analgesia. To test this hypothesis, mice with diet-induced obesity were treated with morphine at 10 mg/kg subcutaneously and with leptin or placebo intranasally. Sleep and breathing were recorded by barometric plethysmography, and pain sensitivity was measured by the tail-flick test. Excitatory postsynaptic currents were recorded in vitro from hypoglossal motor neurons after the application of the μ-opioid receptor agonist [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin and leptin. Morphine dramatically increased the frequency of apneas and greatly increased the severity of hypoventilation and obstructive sleep apnea. Leptin decreased the frequency of apneas, improved obstructive sleep apnea, and completely reversed hypoventilation, whereas morphine analgesia was enhanced. Our in vitro studies demonstrated that [D-Ala(2), N-MePhe(4), Gly-ol]-enkephalin reduced the frequency of excitatory postsynaptic currents in hypoglossal motoneurons and that application of leptin restored excitatory synaptic neurotransmission. Our findings suggest that intranasal leptin may prevent opioid respiratory depression during sleep in patients with obesity receiving opioids without reducing analgesia.

Introduction Obstructive sleep apnea (OSA) is characterized by recurrent periods of upper airway obstruction. The prevalence of OSA exceeds 50% in obese individuals and in 10–20% of obese patients OSA coexists with obesity hypoventilation syndrome (OHS) defined as daytime hypercapnia and hypoventilation during sleep attributed to the depressed control of breathing. There is no effective pharmacotherapy for OSA and OHS. Leptin is a potent respiratory stimulant and a potential therapeutic candidate. However, diet-induced obesity (DIO) results in reduced permeability of the blood-brain barrier (BBB) for leptin. Previous studies have shown that the BBB can be penetrated by exosomes, natural nanoparticles that can be used as drug delivery vehicles. In this study, we aimed to determine if exosomes overcome the BBB and treat OSA and OHS in DIO mice. Methods o examine the ability of exosomes to cross the BBB, male, lean (n=5) and DIO (n=5) C57BL/6J mice were injected with fluorescent exosomes or saline into the lateral tail vein. After 4h fluorescent exosomes biodistribution was evaluated by an in vitro imaging system (IVIS). Saline injected mice images were used for background adjustment. A separate subgroup of male, DIO (n=10) and lean (n=10) mice were headmounted with EEG and nuchal EMG leads. Sleep studies were performed in a plethysmography chamber and mice received saline, empty exosomes, free leptin, or leptin-loaded exosomes in a crossover manner. Results Exosomes were successfully delivered to the brain and the transport across the BBB was more efficient in DIO mice with 2-times greater relative fluorescence units measured in DIO when compared to lean mice (p Conclusion We demonstrated that exosomes overcome the BBB and that leptin-loaded exosomes treat OSA and OHS in DIO mice. Support (if any) R01HL 128970, R01HL 138932, R61 HL156240, U18 DA052301, FAPESP 2018/08758-3

The present disclosure generally relates to compositions and methods of treating opioid-induced respiratory depression in a subject in need thereof, the method comprising administering leptin.

Obstructive sleep apnea (OSA) is a highly prevalent disease characterized by recurrent closure of the upper airway during sleep. It has a complex pathophysiology involving four main phenotypes. An abnormal upper airway anatomy is the key factor that predisposes to sleep-related collapse of the pharynx, but it may not be sufficient for OSA development. Non-anatomical traits, including (1) a compromised neuromuscular response of the upper airway to obstruction, (2) an unstable respiratory control (high loop gain), and (3) a low arousal threshold, predict the development of OSA in association with anatomical abnormalities. Current therapies for OSA, such as continuous positive airway pressure (CPAP) and oral appliances, have poor adherence or variable efficacy among patients. The search for novel therapeutic approaches for OSA, including pharmacological agents, has been pursued over the past years. New insights into OSA pharmacotherapy have been provided by preclinical studies, which highlight the importance of appropriate use of animal models of OSA, their applicability, and limitations. In the present review, we discuss potential pharmacological targets for OSA discovered using animal models.

Patient-Centered Design (PCD) is a particular type of User-Centered Design (UCD), where the end-user is a patient that will use an Information and Communications Technology (ICT) solution for healthcare. It focuses on needs, wants, and skills of the product's primary user and implies involving end-users in the decision-making and development process of the solution. e-Therapy aims to provide support to therapy sessions through ICT solutions. It has grown in the last years, and in the mental health arena is being used for specific therapeutic contexts. It is an especially difficult environment due to specificities of the patients' conditions and the physical access to patients being restricted and, sometimes, not even possible. Thus, a PCD approach can be accomplished through the health professionals involved, applying some of the most well known methods of UCD: interviews, questionnaires, focus groups, and participatory design. eSchi is an e-Therapy tool that complements traditional practices for the cognitive rehabilitation and training of schizophrenic patients. It was successfully developed using a PCD approach.

The harmony of the facial profile is widely influenced by the height and form of the nasal dorsum. A few millimeters can make the lateral view aesthetically more or less pleasing and adequate in a subject's face. Professionals working with facial aesthetics should focus not only on the surgical techniques for proposed outcomes, but also with the subtleties and subjectivity that characterize aesthetic concepts and judgment.Material and MethodsA prospective survey to evaluate the preferences of a group of healthcare professionals working with facial aesthetics, a group of fine artists, and lay people about the best nasal radix height; the survey involved comparing 3 different nasal radix heights using computer-altered photographs of women with measurements close to the Caucasian standard.Results and conclusionThe lowest position of the nasal radix - close to the height of the pupil - was preferred (53%), followed by the middle position (superior crease of the eye). The highest position, resembling classic Greek statues, was considered the worst. The authors aos evaluated the effect of age, gender, and educational level on the choice of the best and worst female profiles.