A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila.

Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the dec2 gene (dec2P384R) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the dec2P384R mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep. To test this directly, we used a Drosophila model to study the effects of the dec2P384R mutation on animal health. Expression of human dec2P384R in fly sleep neurons was sufficient to mimic the short sleep phenotype and, remarkably, dec2P384R mutants lived significantly longer with improved health despite sleeping less. The improved physiological effects were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Moreover, we provide evidence that upregulation of pro-health pathways also contributes to the short sleep phenotype, and this phenomenon may extend to other pro-longevity models.

A familial natural short sleep mutation promotes healthy aging and extends lifespan in Drosophila.

Sleep loss typically imposes negative effects on animal health. However, humans with a rare genetic mutation in the dec2 gene ( dec2 P384R ) present an exception; these individuals sleep less without the usual effects associated with sleep deprivation. Thus, it has been suggested that the dec2 P384R mutation activates compensatory mechanisms that allows these individuals to thrive with less sleep. To test this directly, we used a Drosophila model to study the effects of the dec2 P384R mutation on animal health. Expression of human dec2 P384R in fly sleep neurons was sufficient to mimic the short sleep phenotype and, remarkably, dec2 P384R mutants lived significantly longer with improved health despite sleeping less. The improved physiological effects were enabled, in part, by enhanced mitochondrial fitness and upregulation of multiple stress response pathways. Moreover, we provide evidence that upregulation of pro-health pathways also contributes to the short sleep phenotype, and this phenomenon may extend to other pro-longevity models.

Rapid and effective fusion repair of severed digital nerves using neurorrhaphy and bioengineered solutions including polyethylene glycol: A case report.

Peripheral nerve injuries (PNIs) that consist of simple nerve severance often result in severe motor impairment and permanent loss of function. Such patients face significant costs and pose major burdens to healthcare systems. Currently, the most promising surgical technique to achieve the best clinical outcome after such PNIs is immediate primary coaptation of severed nerve ends by microsutures (neurorrhaphy). However, recovery is often poor and delayed for many months due to Wallerian degeneration (WD) and slow (1-2 mm/day) axonal outgrowths from severed proximal axons that may not properly reinnervate denervated afferent/efferent targets that have atrophied. In contrast, recent pre-clinical studies using polyethylene glycol (PEG) to facilitate primary nerve repair have greatly improved the rate and extent of sensory and motor recovery and prevented much WD and muscle atrophy. That is, PEG-fused axons rapidly establish proximal-distal axoplasmic/axolemmal continuity, which do not undergo WD and maintain the structure and function of neuromuscular junction (NMJ). PEG-fused axons rapidly reinnervate denervated NMJs, thereby preventing muscle atrophy associated with monthslong denervation due to slowly regenerating axonal outgrowths. We now describe PEG-mediated fusion repair of a digital nerve in each of two patients presenting with a digital laceration resulting in total loss of sensation. The first patient's tactile perception improved markedly at 3 days postoperatively (PO). Two-point discrimination improved from greater than 10 mm at initial presentation to 4 mm at 11-week PO, and the Semmes-Weinstein monofilament score improved from greater than 6.65 to 2.83 mm, a near-normal level. The second patient had severe PO edema and scar development requiring a hand compression glove and scar massage, which began improving at 11-week PO. The sensory function then improved for 4 months PO, with both two-point discrimination and Semmes-Weinstein scores approaching near-normal levels at the final follow-up. These case study data are consistent with data from animal models. All these data suggest that PEG-fusion technologies could produce a paradigm shift from the current clinical practice of waiting days to months to repair ablation PNIs with autografts, anucleated nerve allografts, or conduits in which the patient outcome is solely dependent upon axon regeneration over months or years.

Optimizing Tourniquet Pressure in Upper Extremity Surgery.

Background: Pneumatic tourniquet is an effective tool to achieve hemostatic control of the surgical field in upper extremity (UE) operations. Elevated pressures have been associated with adverse effects despite various methods of pressure determination. We aim to demonstrate the usage of reduced tourniquet pressures and examine factors associated with achieving reduced pressures. Methods: A prospective study was conducted (2016-2018) at a Level 1 Trauma Center and an Outpatient Surgical Center, totaling 226 operations, involving a reduction of cuff pressures over time from a standard baseline of limb occlusion pressure for UE operations. Results: A gradual reduction of pressures was successfully achieved with a mean pressure of 187 mmHg and average time of tourniquet application being 25 minutes. We found chronological surgical number and patient BMI to be significantly associated with tourniquet pressure (p < 0.05). 4.5% of cases resulted in breakthrough bleeding, but did not reliably occur with any pressure thresholds, patient demographics, or operative factors (p > 0.05, for all). Conclusions: Reduced tourniquet pressures can mitigate complications associated with tourniquet use. Our research shows reduced pressures are successful in maintaining field visibility and we encourage an adoption of pressures below 200 mm Hg in most procedures that require a tourniquet.

Surgeon-Controlled Comparison of Direct-to-Implant and 2-Stage Tissue Expander-Implant Immediate Breast Reconstruction Outcomes.

BACKGROUND: Current literature comparing outcomes of immediate breast reconstruction using direct-to-implant (DTI) single-stage and 2-stage tissue expanders (TEs) is conflicting. This study compared overall outcomes and determined predictive patient factors associated with higher complication rates. METHODS: After institutional review board approval, a retrospective cohort study of consecutive patients who underwent immediate breast reconstruction from 2010 to 2014 at a single hospital was performed. Demographic data and complications were recorded and compared using univariate analysis. Infection was defined as any patient receiving antibiotics beyond the expected postoperative course or restarting antibiotics for a suspected infection. RESULTS: Seventy-nine breasts (50 patients) underwent immediate breast reconstruction using tissue expansion, and 117 breasts (69 patients) underwent immediate breast reconstruction using the DTI technique. Overall complications, infection rate, and rate of aesthetic revisions were higher in the TE group compared with the DTI group. There was no difference in rates of seroma, hematoma, and mastectomy skin flap necrosis between the 2 groups. Infectious complications were significantly higher in patients with body mass index of greater than 30 who underwent TE-based reconstruction than those who underwent DTI-based reconstruction. CONCLUSIONS: Single-stage DTI immediate breast reconstruction has less overall complications than 2-stage TE-based immediate reconstruction. Direct-to-implant immediate breast reconstruction may provide favorable outcomes in patients with body mass index of greater than 30.