Rapid tissue engineering of biomimetic human corneal limbal crypts with 3D niche architecture

Limbal epithelial stem cells are responsible for the maintenance of the human corneal epithelium and these cells reside in a specialised stem cell niche. They are located at the base of limbal crypts, in a physically protected microenvironment in close proximity to a variety of neighbouring niche cells. Design and recreation of elements of various stem cell niches have allowed researchers to simplify aspects of these complex microenvironments for further study in vitro. We have developed a method to rapidly and reproducibly create bioengineered limbal crypts (BLCs) in a collagen construct using a simple one-step method. Liquid is removed from collagen hydrogels using hydrophilic porous absorbers (HPAs) that have custom moulded micro-ridges on the base. The resulting topography on the surface of the thin collagen constructs resembles the dimensions of the stromal crypts of the human limbus. Human limbal epithelial cells seeded onto the surface of the constructs populate these BLCs and form numerous layers with a high proportion of the cells lining the crypts expressing putative stem cell marker, p63α. The HPAs are produced using a moulding process that is flexible and can be adapted depending on the requirements of the end user. Creation of defined topographical features using this process could be applicable to numerous tissue-engineering applications where varied 3-dimensional niche architectures are required.     

Effects of extended-release quetiapine fumarate on long-term functioning and sleep quality in patients with Generalized Anxiety Disorder (GAD): Data from a randomized-withdrawal,placebo-controlled maintenance study

Background

This analysis evaluated effects of quetiapine XR maintenance treatment on functioning and sleep in patients with GAD.

Methods

Analysis of patient-reported data from a randomized-withdrawal, double-blind, placebo-controlled study of quetiapine XR monotherapy in GAD. Following open-label run-in (4–8 weeks) and a 12–18-week stabilization phase (quetiapine XR 50, 150, or 300 mg/day), eligible patients were randomized to continue on quetiapine XR or receive placebo for up to 52 weeks. Primary variable was time to an anxiety event. Secondary variables included the Sheehan Disability Scale (SDS) and Pittsburgh Sleep Quality Index (PSQI).

Results

In total, 432 patients were randomized (quetiapine XR, N=216; placebo, N=216). The risk of an anxiety event was significantly reduced for quetiapine XR vs. placebo (HR 0.19; 95% CI 0.12, 0.31; p<0.001). Quetiapine XR was more effective than placebo at maintaining SDS total scores (LSM change: −0.19 vs. 1.01; p=0.017) and non-work-related SDS domain score ‘family life/home responsibilities’ (−0.13 vs. 0.32; p=0.011), but not ‘social life’ (0.05 vs. 0.34; p=0.114). Quetiapine XR was more effective than placebo at maintaining the work-related SDS domain score ‘days lost’ (−0.05 vs. 0.11; p=0.027), but not ‘work/school’ (−0.10 vs. 0.29; p=0.051) or ‘days underproductive’ (0.06 vs. 0.13; p=0.619). PSQI global scores were reduced from randomization with quetiapine XR vs. placebo (0.39 vs. 1.60; p<0.001).

Limitations

Lack of active-comparator arm, exclusion of patients with comorbid depression.

Conclusions

In patients with GAD, long-term treatment with quetiapine XR (50–300 mg/day) monotherapy was effective at maintaining improvements in functioning and sleep quality.     

The association between sleep spindles and IQ in healthy school-age children

Recent studies have suggested that sleep is associated with IQ measures in children, but the underlying mechanism remains unknown. An association between sleep spindles and IQ has been found in adults, but only two previous studies have explored this topic in children. The goal of this study was to examine whether sleep spindle frequency, amplitude, duration and/or density were associated with performance on the perceptual reasoning, verbal comprehension, working memory, and processing speed subscales of the Wechsler Intelligence Scale for Children-IV (WISC-IV). We recruited 29 typically developing children 7–11 years of age. We used portable polysomnography to document sleep architecture in the natural home environment and evaluated IQ. We found that lower sleep spindle frequency was associated with better performance on the perceptual reasoning and working memory WISC-IV scales, but that sleep spindle amplitude, duration and density were not associated with performance on the IQ test.     

Diagnosing Autism Spectrum Disorder in Toddlers Born Very Preterm: Estimated Prevalence and Usefulness of Screeners and the Autism Diagnostic Observation Schedule (ADOS)

This study estimated ASD prevalence in a cohort of 3-year-old very preterm children (N?=?55) and investigated the usefulness of parent-reported ASD screeners and the ADOS-2. 12.7% received an ASD diagnosis by clinical judgment based on DSM-5 criteria. An additional 14.5% were classified as having a broader-autism-phenotype outcome. Sensitivity values for the screeners were poor, whereas specificity values ranged from poor to excellent. The ADOS-2 identified all children with ASD and had a fair specificity. These findings confirm the elevated ASD prevalence made by previous studies with preterm children but also highlight the challenges of successfully identifying ASD in this at-risk group. Caution is warranted when interpreting results of ASD instruments with the currently available cut-off scores and algorithms, especially when developmental challenges are present.

     

A Comprehensive,Model-Based Review of Vaccine and Repeat Infection Trials for Filariasis

SUMMARY

Filarial worms cause highly morbid diseases such as elephantiasis and river blindness. Since the 1940s, researchers have conducted vaccine trials in 27 different animal models of filariasis. Although no vaccine trial in a permissive model of filariasis has provided sterilizing immunity, great strides have been made toward developing vaccines that could block transmission, decrease pathological sequelae, or decrease susceptibility to infection. In this review, we have organized, to the best of our ability, all published filaria vaccine trials and reviewed them in the context of the animal models used. Additionally, we provide information on the life cycle, disease phenotype, concomitant immunity, and natural immunity during primary and secondary infections for 24 different filaria models.     

Motivational Profiles for Physical Activity Practice in Adults with Type 2 Diabetes: A Self-Determination Theory Perspective

Drawing on Self-Determination Theory, this study explored the motivational profiles toward Physical Activity (PA) among adults with type 2 diabetes and the relationships between motivational profile, perceived competence and PA. Participants were 350 men and women (Mean age 62.77 years) who were interviewed on their motivations toward PA, perceived level of competence to practice, and PA practice. Cluster analyses reveal the existence of three distinct profiles: “High Combined” (ie, high scores on motivations ranging from intrinsic to external regulation, moderate level on amotivation), “Self-Determined” (ie, high scores on intrinsic, integrated, and identified regulations; low scores on other regulations), and “Moderate” (ie, moderate scores on all regulations). Participants with “High Combined” and “Self-Determined” profiles reported higher perceived competence and longer leisure-time PA practice in comparison to those with a “Moderate” profile. This study highlights the necessity of adopting a person-centered approach to better understand motivation toward PA among type 2 diabetics.     

Strategies to Promote Social Connections Among Older Adults During “Social Distancing” Restrictions

Older age and medical comorbidity are factors associated with more severe illness and risk of death due to COVID-19 infection. Social distancing is an important public health strategy for controlling the spread of the virus and minimizing its impact on the older adult population. It comes at a cost, however. Loneliness is associated with myriad adverse health outcomes, one of which is impaired immune functioning, which adds even greater risk for coronavirus infection, complications and death. Older adults, therefore, are at compound risk, making effective management of loneliness and social isolation in our older patients a high priority target for preventive intervention. In this paper, the authors describe a cognitive-behavioral framework for social connectedness, including evidence-informed strategies clinicians can use to help patients develop a “Connections Plan” to stay connected and promote their social, mental, and physical health during “social distancing” restrictions. This set of strategies can be provided during brief (30 minute) telephone sessions and is analogous to creating a “Safety Plan” for suicide risk. The approach is illustrated with three case examples.