Pilot randomized controlled trial of eHealth cognitive-behavioral therapy for insomnia among Spanish-speaking breast cancer survivors.

Cognitive-Behavioral Therapy for Insomnia (CBT-I) is the gold-standard treatment for insomnia, which is common among breast cancer survivors (BCS). This pilot randomized controlled trial tested the first CBT-I intervention for Spanish-speaking BCS delivered using eHealth. Participants (N = 30) were Spanish-speaking BCS with insomnia symptoms recruited in Puerto Rico and randomized to a 6-week eHealth CBT-I group intervention or a waitlist control. Primary outcomes were acceptability (recruitment, treatment satisfaction) and feasibility (retention, attendance). Secondary outcomes were group differences in sleep outcomes post-treatment (i.e., insomnia symptoms, sleep disturbance, sleep efficiency). Recruitment (95%) and retention (97%) were excellent. All CBT-I participants (100%) attended ≥ 3 of 6 sessions. Satisfaction with CBT-I was acceptable. Post-intervention, there were medium to large group differences for average insomnia symptoms (d = 1.02), sleep disturbance (d = 1.25), and sleep efficiency (d = 0.77) favoring CBT-I. There were small/medium to medium/large group differences for the proportion of participants with clinically significant insomnia symptoms (d = 0.52), sleep disturbance (d = 0.67), and low sleep efficiency (d = 0.33) favoring CBT-I. Spanish-language eHealth CBT-I for BCS was acceptable and feasible and showed preliminary efficacy.ClinicalTrials.gov TRN: NCT04101526 (Posted September 24, 2019).

Anesthetic considerations in myofibrillar myopathy.

Myofibrillar myopathy (MFM) is a relatively newly recognized genetic disease that leads to progressive muscle deterioration. MFM has a varied phenotypic presentation and impacts cardiac, skeletal, and smooth muscles. Affected individuals are at increased risk of respiratory failure, significant cardiac conduction abnormalities, cardiomyopathy, and sudden cardiac death. In addition, significant skeletal muscle involvement is common, which may lead to contractures, respiratory insufficiency, and airway compromise as the disease progresses. This study is the first report of anesthetic management of a patient with MFM. We report multiple anesthetic encounters of a child with genetically confirmed BAG3-myopathy, a subtype of MFM with severe childhood disease onset. A review of the anesthetic implications of the disease is provided, with specific exploration of possible susceptibility to malignant hyperthermia, rhabdomyolysis, and sensitivity to other anesthetic agents.

Epithelial-derived brain-derived neurotrophic factor is required for gustatory neuron targeting during a critical developmental period.

Brain-derived neurotrophic factor (BDNF) is expressed in epithelial targets of gustatory neurons (i.e., fungiform papillae) before their innervation, and BDNF overexpression in nontaste regions of the tongue misdirects gustatory axons to these sites, suggesting that BDNF is necessary for gustatory axons to locate and innervate their correct targets during development. To test this hypothesis, we examined the targeting of taste neurons in BDNF-null mice (bdnf(-/-)). Analysis of bdnf(-/-) mice using a combination of DiI labeling and electron microscopy revealed that taste regions were not innervated by gustatory axons. Instead, branching was increased and many nontaste regions were innervated. The increased branching by gustatory axons in these animals was facilitated by neurotrophin 4 (NT4), because branching was virtually eliminated in bdnf(-/-)/nt4(-/-) mice. No abnormalities in gustatory innervation patterns and targeting were observed in nt4(-/-) mice. Conditional removal of BDNF selectively in epithelial cells disrupted targeting at the tongue tip, where gene recombination removed bdnf by embryonic day 13.5 (E13.5). However, innervation patterns were normal in the midregion and caudal portions of the tongue, where gene recombination did not occur until E14.5. These findings demonstrate that BDNF derived from gustatory epithelia is required for gustatory axons to correctly locate and innervate fungiform papillae. In addition, they show that BDNF-mediated targeting is restricted to a critical period of development, on or before E13.5.

Distinct Yellowfin Tuna (Thunnus albacares) Stocks Detected in Western and Central Pacific Ocean (WCPO) Using DNA Microsatellites.

The yellowfin tuna, Thunnus albacares (Bonnaterre, 1788), covers majority of the Philippines' tuna catch, one of the major fisheries commodities in the country. Due to its high economic importance sustainable management of these tunas has become an imperative measure to prevent stock depletion. Currently, the Philippine yellowfin tuna is believed to be part of a single stock of the greater WCPO though some reports suggest otherwise. This study therefore aims to establish the genetic stock structure of the said species in the Philippines as compared to Bismarck Sea, Papua New Guinea using nine (9) DNA microsatellite markers. DNA microsatellite data revealed significant genetic differentiation between the Philippine and Bismarck Sea, Papua New Guinea yellowfin tuna samples. (FST = 0.034, P = 0.016), which is further supported by multilocus distance matrix testing (PCoA) and model-based clustering (STRUCTURE 2.2).With these findings, this study posits that the yellowfin tuna population in the Philippines is a separate stock from the Bismarck Sea population. These findings add evidence to the alternative hypothesis of having at least 2 subpopulations of yellowfin tuna in the WCPO and calls for additional scientific studies using other parameters to investigate this. Accurate population information is necessary in formulating a more appropriate management strategy for the sustainability of the yellowfin tuna not only in the Philippines but also in the WCPO.

Refinement of innervation accuracy following initial targeting of peripheral gustatory fibers.

During development, axons of the chorda tympani nerve navigate to fungiform papillae where they penetrate the lingual epithelium, forming a neural bud. It is not known whether or not all chorda tympani axons initially innervate fungiform papillae correctly or if mistakes are made. Using a novel approach, we quantified the accuracy with which gustatory fibers successfully innervate fungiform papillae. Immediately following initial targeting (E14.5), innervation was found to be incredibly accurate: specifically, 94% of the fungiform papillae on the tongue are innervated. A mean of five papillae per tongue were uninnervated at E14.5, and the lingual tongue surface was innervated in 17 places that lack fungiform papillae. To determine if these initial errors in papillae innervation were later refined, innervation accuracy was quantified at E16.5 and E18.5. By E16.5 only two papillae per tongue remained uninnervated. Innervation to inappropriate regions was also removed, but not until later, between E16.5 and E18.5 of development. Therefore, even though gustatory fibers initially innervate fungiform papillae accurately, some errors in targeting do occur that are then refined during later embryonic periods. It is likely that trophic interactions between gustatory neurons and developing taste epithelium allow appropriate connections to be maintained and inappropriate ones to be eliminated.

Epithelial overexpression of BDNF and NT4 produces distinct gustatory axon morphologies that disrupt initial targeting.

Most fungiform taste buds fail to become innervated when BDNF or NT4 is overexpressed in the basal layer of tongue epithelium. Here, we examined when and how overexpression of BDNF and NT4 disrupt innervation to fungiform papillae. Overexpression of either factor disrupted chorda tympani innervation patterns either before or during the initial innervation of fungiform papillae. NT4 and BDNF overexpression each disrupted initial innervation by producing different gustatory axon morphologies that emerge at distinct times (E12.5 and E14.5, respectively). Chorda tympani nerve branching was reduced in NT4 overexpressing mice, and neuronal fibers in these mice were fasciculated and remained below the epithelial surface, as if repelled by NT4 overexpression. In contrast, many chorda tympani nerve branches were observed near the epithelial surface in mice overexpressing BDNF, and most were attracted to and invaded non-taste filiform papillae instead of gustatory papillae. These results suggest that BDNF, but not NT4, normally functions as a chemoattractant that allows chorda tympani fibers to distinguish their fungiform papillae targets from non-gustatory epithelium. Since BDNF and NT4 both signal through the p75 and TrkB receptors, trophin-specific activation of different internal signaling pathways must regulate the development of the distinct gustatory axon morphologies in neurotrophin-overexpressing mice.

Adenosine A(2A) receptors mediate hypoxic inhibition of fetal breathing in sheep.

OBJECTIVE: Hypoxia inhibits fetal breathing through activation of central adenosine (ADO) receptors that modulate fetal behavioral state. This study was designed to determine whether adenosine A(1) and/or A(2A)receptor subtypes mediate the depressant effects of hypoxia. STUDY DESIGN: In 14 chronically catheterized fetal sheep (>0.8 term), hypoxemia was induced by having the ewe breathe a gas mixture of 9% oxygen for 1 hour. During hypoxia, the fetus was infused intra-arterially with a vehicle or an antagonist for adenosine A(1) or A(2A) receptors. Statistical analysis was performed by using analysis of variance with Tukey's least significant difference criterion. RESULTS: Fetal isocapnic hypoxemia (PaO(2): control, approximately 24 mm Hg; hypoxia, approximately 14 mm Hg) virtually eliminated rapid eye movements and breathing when the fetus was infused with vehicle or the A(1) receptor antagonist. In contrast, adenosine A(2A) receptor blockade abolished the hypoxia-induced arrest of rapid eye movements and breathing. CONCLUSION: Hypoxic inhibition of rapid eye movements and breathing is critically dependent on activation of adenosine A(2A) receptors.