Notes

Dysregulation from the epithelial buffer by environmental and other exogenous aspects.
Saliva, while often taken for granted, is indispensable for oral health and overall well-being, as inferred from the significant impairments suffered by patients with salivary gland dysfunction. Here, we show that treatment with several structurally distinct PAN-PDE4 inhibitors, but not a PDE3 inhibitor, induces saliva secretion in mice, indicating it is a class-effect of PDE4 inhibitors. In anesthetized mice, while neuronal regulations are suppressed, PDE4 inhibition potentiates a β-adrenoceptor-induced salivation, that is ablated by the β-blocker Propranolol and is absent from homozygous ΔF508-CFTR mice lacking functional CFTR. These data suggest that PDE4 acts within salivary glands to gate saliva secretion that is contingent upon the cAMP/PKA-dependent activation of CFTR. Indeed, PDE4 contributes the majority of total cAMP-hydrolytic capacity in submandibular-, sublingual-, and parotid glands, the three major salivary glands of the mouse. In awake mice, PDE4 inhibitor-induced salivation is reduced by CFTR deficiency or β-blockers, but also by the muscarinic blocker Atropine, suggesting an additional, central/neuronal mechanism of PDE4 inhibitor action. The PDE4 family comprises four subtypes, PDE4A-D. Ablation of PDE4D, but not PDE4A-C, produced a minor effect on saliva secretion, implying that while PDE4D may play a predominant role, PDE4 inhibitor-induced salivation results from the concurrent inactivation of multiple (at least two) PDE4 subtypes. Manogepix Taken together, our data reveal a critical role for PDE4/PDE4D in controlling CFTR function in an in vivo model and in inducing salivation, hinting at a therapeutic potential of PDE4 inhibition for cystic fibrosis and conditions associated with xerostomia.The class Bivalvia is a highly successful and ancient taxon including ∼25,000 living species. During their long evolutionary history bivalves adapted to a wide range of physicochemical conditions, habitats, biological interactions, and feeding habits. Bivalves can have strikingly different size, and despite their apparently simple body plan, they evolved very different shell shapes, and complex anatomic structures. One of the most striking features of this class of animals is their peculiar mitochondrial biology some bivalves have facultatively anaerobic mitochondria that allow them to survive prolonged periods of anoxia/hypoxia. Moreover, more than 100 species have now been reported showing the only known evolutionarily stable exception to the strictly maternal inheritance of mitochondria in animals, named doubly uniparental inheritance. Mitochondrial activity is fundamental to eukaryotic life, and thanks to their diversity and uncommon features, bivalves represent a great model system to expand our knowledge about mitochondrial biology, so far limited to a few species. We highlight recent works studying mitochondrial biology in bivalves at either genomic or physiological level. A link between these two approaches is still missing, and we believe that an integrated approach and collaborative relationships are the only possible ways to be successful in such endeavour.
Cognitive behavioral therapy for insomnia (CBTI) targets changing dysfunctional sleep-related beliefs. The impact of these changes on daytime functioning in older adults is unknown.

We examined whether changes in sleep-related beliefs from pre- to post-CBTI predicted changes in sleep and other outcomes in older adults.

Data included 144 older veterans with insomnia from a randomized controlled trial testing CBTI. Sleep-related beliefs were assessed with the Dysfunctional Beliefs and Attitudes about Sleep-16 (DBAS-16, subscales Consequences, Worry/Helplessness, Sleep Expectations, Medication). Outcomes included sleep diary variables, actigraphy-measured sleep efficiency, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Flinders Fatigue Scale (FFS), Patient Health Questionnaire-9, and health-related quality of life. Analyses compared slope of change in DBAS subscales from baseline to posttreatment between CBTI and control, and assessed the relationship between DBAS change and the slope of change in outcomes from baseline to 6 months.

Compared to controls, the CBTI group demonstrated stronger associations between improvement in DBAS-Consequences and subsequent improvement in PSQI, ISI, ESS, and FFS. The CBTI group also demonstrated stronger associations between improvement in DBAS-Worry/Helplessness and subsequent improvements in PSQI, ISI, and FFS; improvements in DBAS-Medication and PSQI; and improvements in DBAS-Sleep Expectations and wake after sleep onset (sleep diary) and FFS (all p < .05).

Significant reduction in dysfunctional sleep-related beliefs following CBTI in older adults predicted improvement in several outcomes of sleep and daytime functioning. This suggests the importance of addressing sleep-related beliefs for sustained improvement with CBTI in older veterans.

ClinicalTrials.gov Identifier NCT00781963.
ClinicalTrials.gov Identifier NCT00781963.Humans can grasp the "average" feature of a visual ensemble quickly and effortlessly. However, it is largely unknown what is the exact form of the summary statistic humans perceive and it is even less known whether this form can be changed by feedback. Here we borrow the concept of loss function to characterize how the summary perception is related to the distribution of feature values in the ensemble, assuming that the summary statistic minimizes a virtual expected loss associated with its deviation from individual feature values. In two experiments, we investigated a random-dot motion estimation task to infer the virtual loss function implicit in ensemble perception and see whether it can be changed by feedback. On each trial, participants reported the average moving direction of an ensemble of moving dots whose distribution of moving directions was skewed. In Experiment 1, where no feedback was available, participants' estimates fell between the mean and the mode of the distribution and were closer to the mean. In particular, the deviation from the mean and toward the mode increased almost linearly with the mode-to-mean distance. The pattern was best modeled by an inverse Gaussian loss function, which punishes large errors less heavily than the quadratic loss function does. In Experiment 2, we tested whether this virtual loss function can be altered by feedback. Two groups of participants either received the mode or the mean as the correct answer. After extensive training up to five days, both groups' estimates moved slightly towards the mode. That is, feedback had no specific influence on participants' virtual loss function. To conclude, the virtual loss function in the summary perception of motion is close to inverse Gaussian, and it can hardly be changed by feedback.The vision sciences literature contains a large diversity of experimental and theoretical approaches to the study of visual attention. We argue that this diversity arises, at least in part, from the field's inability to unify differing theoretical perspectives. In particular, the field has been hindered by a lack of a principled formal framework for simultaneously thinking about both optimal attentional processing and capacity-limited attentional processing, where capacity is limited in a general, task-independent manner. Here, we supply such a framework based on rate-distortion theory (RDT) and optimal lossy compression. Our approach defines Bayes-optimal performance when an upper limit on information processing rate is imposed. In this article, we compare Bayesian and RDT accounts in both uncued and cued visual search tasks. We start by highlighting a typical shortcoming of unlimited-capacity Bayesian models that is not shared by RDT models, namely, that they often overestimate task performance when information-processing demands are increased. Next, we reexamine data from two cued-search experiments that have previously been modeled as the result of unlimited-capacity Bayesian inference and demonstrate that they can just as easily be explained as the result of optimal lossy compression. To model cued visual search, we introduce the concept of a "conditional communication channel." This simple extension generalizes the lossy-compression framework such that it can, in principle, predict optimal attentional-shift behavior in any kind of perceptual task, even when inputs to the model are raw sensory data such as image pixels. To demonstrate this idea's viability, we compare our idealized model of cued search, which operates on a simplified abstraction of the stimulus, to a deep neural network version that performs approximately optimal lossy compression on the real (pixel-level) experimental stimuli.
PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum.

The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines.

This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as assessed by the investigator on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment of 20 U prabotulinumtoxinA (4 U/0.1 mL freeze-dried formulation injected into 5 target glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety was evaluated throughout the study.

The 352 study patients received a median total dose of 60 U, that is, 3 treatments per year. Fifty-one patients (14.5%) experienced adverse events (AEs) assessed as possibly study drug related; 11.1% experienced study drug-related AEs after the initial treatment. With each RT, progressively lower percentages of patients experienced study drug-related AEs. Six patients (1.7%) experienced study drug-related AEs of special interest 3 eyelid ptosis (0.9%), 2 speech disorder (0.6%), and 1 blepharospasm (0.3%). Seven patients (2.0%) experienced serious AEs; none were study drug related. Of the 2393 samples tested, 2 patients (0.6%) tested positive for antibotulinum toxin antibodies at a single postbaseline visit.

The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was first established in this early phase II study based on a broad range of outcomes.

To identify barriers to safe and effective completion of outpatient parenteral antimicrobial therapy (OPAT) in patients discharged from an academic medical center and to develop targeted solutions to potentially resolve or improve the identified barriers.

A failure modes and effects analysis (FMEA) was conducted by a multidisciplinary OPAT task force to evaluate the processes for patients discharged on OPAT to 2 postdischarge dispositions (1) home and (2) skilled nursing facility (SNF). The task force created 2 process maps and identified potential failure modes, or barriers, to the successful completion of each step. Thirteen and 10 barriers were identified in the home and SNF process maps, respectively. Task force members created 5 subgroups, each developing solutions for a group of related barriers. The 5 areas of focus included (1) the OPAT electronic order set, (2) critical tasks to be performed before patient discharge, (3) patient education, (4) patient follow-up and laboratory monitoring, and (5) SNF communication.
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