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Study Objectives: The purpose of this review is to synthesize the published literature that addresses employer-initiated interventions to improve the sleep of workers and in turn improve health, productivity, absenteeism, and other outcomes that have been associated with sleep disorders or sleep deficiency. Methods: We conducted a systematic search and a selective narrative review of publications in PubMed from 1966 to December 2017. We extracted study characteristics, including the workers' professions, workplace settings and shift work, and workplace interventions focused on worker sleep. Because of the high degree of heterogeneity in design and outcomes, we conducted a narrative review. Results: We identified 219 publications. After restriction to publications with studies of workplace interventions that evaluated the outcomes of sleep duration or quality, we focused on 47 articles. An additional 13 articles were accepted in the pearling process. Most studies employed non-randomized or controlled pretest and posttest designs and self-reported measures of sleep. The most common workplace interventions were educational programs stressing sleep hygiene or fatigue management. Other interventions included timed napping before or after work, urging increased daytime activity levels, modifying workplace environmental characteristics such as lighting, and screening, and referral for sleep disorders treatment. Overall, most reports indicated that employer efforts to encourage improved sleep hygiene and healthier habits result in improvements in sleep duration, sleep quality, and self-reported sleepiness complaints. Conclusions: These studies suggest employer-sponsored efforts can improve sleep and sleep-related outcomes. The existing evidence, although weak, suggests efforts by employers to encourage better sleep habits and general fitness result in self-reported improvements in sleep-related outcomes, and may be associated with reduced absenteeism and better overall quality of life. Candidate workplace strategies to promote sleep health are provided. Citation: Redeker NS, Caruso CC, Hashmi SD, Mullington JM, Grandner M, Morgenthaler TI. Workplace interventions to promote sleep health and an alert, healthy workforce. J Clin Sleep Med 2019;15(4):649–657.

How the brain preserves information about multiple simultaneous items is poorly understood. We report that single neurons can represent multiple stimuli by interleaving signals across time. We record single units in an auditory region, the inferior colliculus, while monkeys localize 1 or 2 simultaneous sounds. During dual-sound trials, we find that some neurons fluctuate between firing rates observed for each single sound, either on a whole-trial or on a sub-trial timescale. These fluctuations are correlated in pairs of neurons, can be predicted by the state of local field potentials prior to sound onset, and, in one monkey, can predict which sound will be reported first. We find corroborating evidence of fluctuating activity patterns in a separate dataset involving responses of inferotemporal cortex neurons to multiple visual stimuli. Alternation between activity patterns corresponding to each of multiple items may therefore be a general strategy to enhance the brain processing capacity, potentially linking such disparate phenomena as variable neural firing, neural oscillations, and limits in attentional/memory capacity. The neural mechanisms through which neurons represent simultaneously presented stimuli are not well understood. Here the authors demonstrate that the two stimuli are alternately encoded through fluctuations in the activity patterns of single neurons.

Pitch and timbre perception are both based on the frequency content of sound, but previous perceptual experiments have disagreed about whether these two dimensions are processed independently from each other. We tested the interaction of pitch and timbre variations using sequential comparisons of sound pairs. Listeners judged whether two sequential sounds were identical along the dimension of either pitch or timbre, while the perceptual distances along both dimensions were parametrically manipulated. Pitch and timbre variations perceptually interfered with each other and the degree of interference was modulated by the magnitude of changes along the un-attended dimension. These results show that pitch and timbre are not orthogonal to each other when both are assessed with parametrically controlled variations.

For the treatment of neurological diseases, achieving sufficient exposure to the brain parenchyma is a critical determinant of drug efficacy. The blood–brain barrier (BBB) functions to tightly control the passage of substances between the bloodstream and the central nervous system, and as such poses a major obstacle that must be overcome for therapeutics to enter the brain. Monoclonal antibodies have emerged as one of the best-selling treatment modalities available in the pharmaceutical market owing to their high target specificity. However, it has been estimated that only 0.1% of peripherally administered antibodies can cross the BBB, contributing to the low success rate of immunotherapy seen in clinical trials for the treatment of neurological diseases. The development of new strategies for antibody delivery across the BBB is thereby crucial to improve immunotherapeutic efficacy. Here, we discuss the current strategies that have been employed to enhance antibody delivery across the BBB. These include (i) focused ultrasound in combination with microbubbles, (ii) engineered bi-specific antibodies, and (iii) nanoparticles. Furthermore, we discuss emerging strategies such as extracellular vesicles with BBB-crossing properties and vectored antibody genes capable of being encapsulated within a BBB delivery vehicle.

Neurotrophic factors are agents with a promising ability to retard progression of neurodegenerative diseases and are effective in slowing photoreceptor degeneration in animal models of retinitis pigmentosa. Here we report a human clinical trial of a neurotrophic factor for retinal neurodegeneration. In this Phase I safety trial, human ciliary neurotrophic factor (CNTF) was delivered by cells transfected with the human CNTF gene and sequestered within capsules that were surgically implanted into the vitreous of the eye. The outer membrane of the encapsulated cell implant is semipermeable to allow CNTF to reach the retina. Ten participants received CNTF implants in one eye. When the implants were removed after 6 months, they contained viable cells with minimal cell loss and gave CNTF output at levels previously shown to be therapeutic for retinal degeneration in rcd1 dogs. Although the trial was not powered to form a judgment as to clinical efficacy, of seven eyes for which visual acuity could be tracked by conventional reading charts, three eyes reached and maintained improved acuities of 10-15 letters, equivalent to two- to three-line improvement on standard Snellen acuity charts. A surgically related choroidal detachment in one eye resulted in a transient acuity decrease that resolved with conservative management. This Phase I trial indicated that CNTF is safe for the human retina even with severely compromised photoreceptors. The approach to delivering therapeutic proteins to degenerating retinas using encapsulated cell implants may have application beyond disease caused by genetic mutations.

The distribution of a species reflects its ecological adaptability and evolutionary history, which is shaped by the environment and represents a dynamic area subject to anthropogenic environmental change. We used the MaxEnt algorithm to construct ecological niche models for four thrush species within the Turdus genus; T. amaurochalinus , T. chiguanco , T. falcklandii and T. rufiventris . These models were used to predict the potential geographic distributions of these species that are expanding their ranges in South America. Using occurrence records, we estimated currently occupied areas for each species. We also identified suitable habitats and projected possible areas to be colonized by the four species at continental scale . Temperature annual range had the highest influence for T. falcklandii , while human modification was the main variable explaining the distribution of the other three species. The potential distribution area ranged from 2.5 million km 2 for T. falcklandii to nearly seven million km 2 for T. amaurochalinus. Large proportions of suitable area remain unoccupied by all four species, being 50% for T. amaurochalinus and T. rufiventris , and about 70% for T. chiguanco and T. falcklandii . Anthropogenic disturbances, such as habitat loss and ecosystem transformation, lead to non-random species extinction and biotic homogenization, highlighting the importance of predictive models as valuable tools for informing mitigation policies and conservation strategies. Thrushes are progressively expanding their ranges, and the colonization of new habitats could bring new challenges.

Celiac disease (CD) is an immune-mediated gluten-sensitive enteropathy. Currently, it affects around 1% of world population, but it is constantly growing. Celiac patients have to follow a strict gluten-free (GF) diet. Beer is one of the most consumed beverages worldwide, but it is not safe for people with CD. It has a gluten content usually above the safe threshold (20 ppm), determined by the official method for hydrolyzed foods (R5-competitive-ELISA). The demand on the market for GF beers is increasingly growing. This review aims to provide a comprehensive overview of different strategies to produce GF beer, highlighting strengths and weaknesses of each approach and taking into account technological and sensory issues. GF cereals or pseudocereals have poor brewing attitudes (if used as main raw material) and give the beer unusual flavour. Instead, enzymatic treatments allow traditional brewing process followed by gluten content reduction. A survey on 185 GF-producing breweries (both industrial and craft) from all over the world have been considered to assess which approach is most used. Beers brewed with GF cereals and pseudocereals (used in well-balanced proportions) are more common than gluten-removed (GR) beers, obtained by enzymatic treatment.

Hypercholesterolemia, which is an increase in total and low-density lipoprotein (LDL) serum cholesterol, is an important risk factor for the development of cardiovascular diseases. Lifestyle modifications underpin any action plan for reducing serum cholesterol. Phytosterols are natural compounds belonging to the triterpenes family. Thanks to their structural analogy with cholesterol, phytosterols have the ability to reduce serum LDL-cholesterol levels. Phytosterols are used to enrich or fortify a broad spectrum of food products. Like unsaturated fatty acids and cholesterol, phytosterols are easily oxidized. Microencapsulation could be a useful tool to overcome this and other drawbacks linked to the use of phytosterols in food fortification. In this review, in addition to explaining the phytosterols’ mechanisms of action, a focus on the use of free and encapsulated phytosterols for the formulation of functional foods, taking also into account both technological and legislative issues, is given.

Background Neural motor control rests on the dynamic interaction of cortical and subcortical regions, which is reflected in the modulation of oscillatory activity and connectivity in multiple frequency bands. Motor control is thought to be compromised in developmental stuttering, particularly involving circuits in the left hemisphere that support speech, movement initiation, and timing control. However, to date, evidence comes from adult studies, with a limited understanding of motor processes in childhood, closer to the onset of stuttering. Methods We investigated the neural control of movement initiation in children who stutter and children who do not stutter by evaluating transient changes in EEG oscillatory activity (power, phase locking to button press) and connectivity (phase synchronization) during a simple button press motor task. We compared temporal changes in these oscillatory dynamics between the left and right hemispheres and between children who stutter and children who do not stutter, using mixed-model analysis of variance. Results We found reduced modulation of left hemisphere oscillatory power, phase locking to button press and phase connectivity in children who stutter compared to children who do not stutter, consistent with previous findings of dysfunction within the left sensorimotor circuits. Interhemispheric connectivity was weaker at lower frequencies (delta, theta) and stronger in the beta band in children who stutter than in children who do not stutter. Conclusions Taken together, these findings indicate weaker engagement of the contralateral left motor network in children who stutter even during low-demand non-speech tasks, and suggest that the right hemisphere might be recruited to support sensorimotor processing in childhood stuttering. Differences in oscillatory dynamics occurred despite comparable task performance between groups, indicating that an altered balance of cortical activity might be a core aspect of stuttering, observable during normal motor behavior.

We described a case of IPEX syndrome successfully controlled with dupilumab, an anti-IL4 receptor alpha subunit inhibitor. IPEX syndrome is a rare and generally fatal genetic disorder characterized by immune dysregulation, polyendocrinopathy and enteropathy, mostly diagnosed in early childhood. Nonetheless, cases reported in the last 20 years demonstrated that IPEX clinical spectrum encompasses more than the classical triad of early-onset intractable diarrhea, type 1 diabetes and eczema. Atypical cases of IPEX include patients with late-onset of symptoms, single-organ involvement, mild disease phenotypes or rare clinical features. A 21-year-old caucasian man presented with immune dysregulation (hypereosinophilia and elevated IgE), protein-losing enteropathy, polyendocrinopathy (thyroiditis, osteoporosis, delayed puberty), weight loss, eczema manifestations and celiac disease. IPEX syndrome was diagnosed because of the presence of a hemizygous mutation in FOXP3 gene (c.543C>T (p.S181S) in the exon 5). During the course of the disease, the patient developed erosive proctitis, pyoderma gangrenosum, and erythema nodosum. Symptoms improved only after enteral and parenteral corticosteroid therapy and the patient soon developed steroid-dependence. Notwithstanding various therapies including azathioprine, sirolimus, tacrolimus, adalimumab, vedolizumab, the patient failed to achieve a good control of symptoms without steroids. Almost exclusive enteral nutrition with a hypoallergenic, milk-protein free, amino acid-based food for special medical purposes. He continued to lose weight (BMI 14.5 kg/m2) with a consequent high limitation of physical activity and a progressive worsening of the quality of life. In consideration of the poor response to conventional immunosuppressants and the presence of type 2 inflammatory manifestations, treatment with dupilumab at an initial dose of 600 mg, followed by a maintenance dose of 300 mg every other week, according to atopic dermatitis labeled dose, was started and combined to oral budesonide 6 mg/day and 6-mercaptopurine 75 mg/day. The patient experienced a rapid improvement in bowel and skin symptoms, leading to a progressive tapering of steroids. By our knowledge, this is the first report of IPEX syndrome successfully treated by antiIL-4/IL-13 therapy. In this case dupilumab demonstrated to be an effective, safe and steroid-sparing option.