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The dysregulation of energy homeostasis in obesity involves multihormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine resistance remains largely unexplored. Murine β3-adrenergic receptor expression in adipocytes is orders of magnitude higher compared with that of other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) and protein expression are dramatically downregulated after ligand exposure (homologous desensitization). β3-Adrenergic receptor downregulation also occurs after high-fat diet feeding, concurrent with catecholamine resistance and elevated inflammation. This downregulation is recapitulated in vitro by TNF-α treatment (heterologous desensitization). Both homologous and heterologous desensitization of Adrb3 were triggered by induction of the pseudokinase TRIB1 downstream of the EPAC/RAP2A/PI-PLC pathway. TRIB1 in turn degraded the primary transcriptional activator of Adrb3, CEBPα. EPAC/RAP inhibition enhanced catecholamine-stimulated lipolysis and energy expenditure in obese mice. Moreover, adipose tissue expression of genes in this pathway correlated with body weight extremes in a cohort of genetically diverse mice and with BMI in 2 independent cohorts of humans. These data implicate a signaling axis that may explain reduced hormone-stimulated lipolysis in obesity and resistance to therapeutic interventions with β3-adrenergic receptor agonists.

Gonadotropin-releasing hormone agonists (GnRHa's) are the standard treatment for children with central precocious puberty (CPP). We aim to present data on available GnRHa options with an easy-to-review table and discuss factors that influence treatment selection. Five GnRHa's are currently FDA-approved and prescribed in the US and published data suggest similar safety and efficacy profiles over the first year of treatment. One- and 3-month intramuscular (IM) leuprolide acetate (LA) have long-term safety and efficacy data and allow for flexible dosing. Six-month IM triptorelin pamoate offers a longer duration of treatment, but without long-term efficacy and outcome data. Six-month subcutaneous (SQ) LA combines a SQ route of injection and long duration of action but lacks long-term efficacy and outcome data. The 12-month SQ histrelin acetate implant avoids injections and offers the longest duration of action, but requires a minor surgical procedure with local or general anesthesia. Factors in treatment selection include route of administration, needle size, injection volume, duration of action, and cost. The current GnRHa landscape provides options with varying benefits and risks, allowing physicians and caregivers to select the most appropriate therapy based on the specific needs and concerns of the child and the caregiver. Agents have different advantages and disadvantages for use, with no one agent displaying superiority.

BackgroundSkin preconditioning prior to and following procedures, has previously been demonstrated to hasten and optimize healing, and decrease the symptoms and signs associated with invasive surgery. These trials involved the use of multiple topical products. In an effort to control costs and to increase patient compliance, a single surgical product was developed, with actives aimed at decreasing swelling, bruising, induration, and internal fibrous banding.ObjectivesThis multi-center trial was designed to measure the efficacy of this single product in these mentioned parameters.MethodsA double-blind, randomized, split body, clinical study was undertaken in 29 patients involving 38 surgical procedures. Assessments included photography, biopsies, ultrasound imaging, and blinded investigator and participant assessments.ResultsDifferentiated results between test comparator sides became apparent at postop day 10-14 (as previously observed). Thus, blinded investigator and participant assessment scores demonstrated statistical significance exclusive to the test product side at postop day 10-14 for ecchymoses and then extending to skin discoloration, edema, induration and subcutaneous fibrous banding, at weeks 3, 4, 6, and 12. Ultrasound evaluation confirmed the earlier dissolution of fibrous banding on the test side in the subcutaneous tissue at the 3-6-week postop period. In addition, biopsies assessing the pre-conditioned period prior to surgery confirmed that the topical test product stimulated a remodeled extracellular matrix without comparative changes on the opposite side.ConclusionsA single peri-surgical product designed for the use with invasive surgery produced significant differences in ecchymosis, skin discoloration, edema, induration and ongoing resolution of fibrous banding over many weeks. This study validation provides an additional adjunct to surgical procedures.Level of evidence 2

Tropical rock lobsters (Panulirus ornatus) are a highly cannibalistic species with intermoult animals predominantly attacking animals during ecdysis (moulting). Rapid, positive characterisation of pre-ecdysis lobsters may open a pathway to disrupt cannibalism. Ecdysial suture line development is considered for pre-ecdysis recognition with suture line definition compared for intermoult and pre-ecdysis lobsters emerged and immerged, using white, near ultraviolet (365 nm), near infrared (850 nm), and specialty SFH 4737 broadband IR LEDs against a reference of intermoult lobsters with no suture line development. Difficulties in acquiring suture line images prompted research into pre-ecdysis characterisation from the lobster’s dorsal carapace, due to its accessibility through a culture vessel’s surface. In this study, a novel low-cost spectral camera was developed by coordinating an IMX219 image sensor, an AS7265x spectral sensor, and four SFH 4737 broadband infrared LEDs through a single-board computer. Images and spectral data from the lobster’s dorsal carapace were acquired from intermoult, pre-ecdysis, and post-ecdysis lobsters. For the first time, suture line definition was found to be enhanced under 850 nm, 365 nm, and SFH 4737 LEDs for immerged lobsters, while the 850 nm LED achieved the best suture line definition of emerged lobsters. Although the spectral camera was unable to characterise pre-ecdysis, its development was validated when a least squares regression for binary classification decision boundary successfully separated 86.7% of post-ecdysis lobsters. Achieving post-ecdysis characterisation is the first time the dorsal carapace surface has been used to characterise a moult stage for palinurid lobsters.

ABSTRACTSerial position effects are often observed within the free recall of unassociated words but also when recalling items from a semantic category like U.S. presidents. We investigated the dynamics of recall for U.S. presidents in younger and older adults to examine potential age-related differences in the organisation of retrieval from semantic long-term memory. Older adults recalled more presidents than younger adults and also demonstrated dual serial position effects such that, in addition to overall serial position effects, primacy (e.g., Eisenhower) and recency presidents (e.g., Obama) within older adults' lifetime were better recalled than presidents from the middle of their lives (e.g., Ford). Additionally, participants initiated recall with the most distinct presidents (highly familiar or memorable presidents like Washington, Obama, Trump), and conditional-response probabilities revealed that presidents from similar eras were recalled in close proximity, indicating that the retrieval of distinct presidents can facilitate memory for presidents from a similar era. Collectively, we demonstrate the potential interplay of the mechanisms that influence the organisation of retrieval such that distinctiveness and temporal contiguity effects may simultaneously impact recall. Specifically, semantic and temporal-contextual associations can drive semantic autobiographical memory and people likely organise retrieval from long-term memory according to familiarity and distinctiveness.

Given natural memory limitations, people can generally attend to and remember high-value over low-value information even when cognitive resources are depleted in older age and under divided attention during encoding, representing an important form of cognitive control. In the current study, we examined whether tasks requiring overlapping processing resources may impair the ability to selectively encode information in dual-task conditions. Participants in the divided-attention conditions of Experiment 1 completed auditory tone-distractor tasks that required them to discriminate between tones of different pitches (audio-nonspatial) or auditory channels (audio-spatial), while studying items in different locations in a grid (visual-spatial) differing in reward value. Results indicated that, while reducing overall memory accuracy, neither cross-modal auditory distractor task influenced participants' ability to selectively encode high-value items relative to a full attention condition, suggesting maintained cognitive control. Participants in Experiment 2 studied the same important visual-spatial information while completing demanding color (visual-nonspatial) or pattern (visual-spatial) discrimination tasks during study. While the cross-modal visual-nonspatial task did not influence memory selectivity, the intra-modal visual-spatial secondary task eliminated participants' sensitivity to item value. These results add novel evidence of conditions of impaired cognitive control, suggesting that the effectiveness of top-down, selective encoding processes is attenuated when concurrent tasks rely on overlapping processing resources.

BackgroundBurns are devastating injuries, carry significant morbidity, and require long-term treatment or multiple reconstructive procedures. Wound healing and secondary insults caused by burn wound conversion are amendable to therapeutic intervention, where ischemia has been cited as one of the major factors (Dermatol Surg. 2008;34:1159-1169). Halting injury progression in the zone of stasis is crucial as conversion creates increased burn surface area and depth, leading to local and systemic consequences (J Burns Wounds. 2006;5:e2). Oxygen-carrying micro/nanobubbles, MNB(O2), offer a novel technology that can be used to effectively deliver oxygen to burn wounds and potentially counteract burn wound ischemia.MethodsTopical irrigation with MNB(O2) of full-thickness burn wounds on a rodent model (n = 3) was compared against saline-treated controls (n = 3). Tissue structure (reduced scattering coefficient, μs'), oxyhemoglobin concentration (cHbO2), and tissue perfusion were quantified over the course of 28 days through spatial frequency domain imaging and laser speckle imaging. Histological samples taken at the end of the experiment were examined for evidence of wound healing.ResultsFindings in this preliminary study showed hastened healing with significant differences in spatial frequency domain imaging-measured μs' during wound healing (days 11-28) in MNB(O2) group. The healing "tipping point" seemed to occur at days 9 to 11 with increased collagen organization and increased cHbO2 occurring around that period confirming the gross healing improvements observed. In addition, histological evidence indicated that only the MNB(O2) burns had reached the remodeling phase by the end of 28-day study period.ConclusionsThese preliminary findings propose the potential of MNB(O2) as a topical method for improving burn wound healing.