Distraction osteogenesis is a bone-regenerative process in which an osteotomy is followed by distraction of the surrounding vascularized bone segments, with formation of new bone within the ...distraction gap. Distraction osteogenesis is efficacious for reconstructing critical sized bony defects in the appendicular and craniofacial skeleton. To provide opportunity to expand applications of distraction osteogenesis, it is important to have a thorough understanding of the underlying molecular biology and physiology of bone development and fracture healing. To accomplish these objectives a review of the literature was performed using search terms "endochondral ossification, intramembranous ossification, craniofacial skeleton, appendicular skeleton, fracture healing, bone development, and distraction osteogenesis." Bones of the craniofacial and appendicular skeleton have distinct mechanisms of embryonic development. The former develops from growth centers of mesenchymal precursors through intramembranous ossification. The latter forms though endochondral ossification in growth plates. However, both endochondral and intramembranous bone share similar master regulatory transcription factors and downstream growth factors. Fracture healing mirrors the pathway by which these bones developed embryonically. In contrast, bone formed by distraction osteogenesis does so by intramembranous ossification, regardless of whether it occurs within the appendicular or craniofacial skeleton. Understanding molecular pathway differences between bone formation by these mechanisms may allow for optimization and expansion of skeletal reconstruction by distraction osteogenesis.
In this paper, we present results from the complete set of cosmic microwave background (CMB) radiation temperature anisotropy observations made with the Arcminute Cosmology Bolometer Array Receiver ...(ACBAR) operating at 150 GHz. We include new data from the final 2005 observing season, expanding the number of detector hours by 210% and the sky coverage by 490% over that used for the previous ACBAR release. As a result, the band-power uncertainties have been reduced by more than a factor of two on angular scales encompassing the third to fifth acoustic peaks as well as the damping tail of the CMB power spectrum. The calibration uncertainty has been reduced from 6% to 2.1% in temperature through a direct comparison of the CMB anisotropy measured by ACBAR with that of the dipole-calibrated WMAP5 experiment. The measured power spectrum is consistent with a spatially flat, CDM cosmological model. We include the effects of weak lensing in the power spectrum model computations and find that this significantly improves the fits of the models to the combined ACBAR+WMAP5 power spectrum. The preferred strength of the lensing is consistent with theoretical expectations. On fine angular scales, there is weak evidence (1.1s) for excess power above the level expected from primary anisotropies. We expect any excess power to be dominated by the combination of emission from dusty protogalaxies and the Sunyaev-Zel'dovich effect (SZE). However, the excess observed by ACBAR is significantly smaller than the excess power at >2000 reported by the CBI experiment operating at 30 GHz. Therefore, while it is unlikely that the CBI excess has a primordial origin; the combined ACBAR and CBI results are consistent with the source of the CBI excess being either the SZE or radio source contamination.
Accumulation of pathological tau in synapses has been identified as an early event in Alzheimer's disease (AD) and correlates with cognitive decline in patients with AD. Tau is a cytosolic axonal ...protein, but under disease conditions, tau accumulates in postsynaptic compartments and presynaptic terminals, due to missorting within neurons, transsynaptic transfer between neurons, or a failure of clearance pathways. Using subcellular fractionation of brain tissue from rTg4510 tau transgenic mice with tauopathy and human postmortem brain tissue from patients with AD, we found accumulation of seed-competent tau predominantly in postsynaptic compartments. Tau-mediated toxicity in postsynaptic compartments was exacerbated by impaired proteasome activity detected by measuring lysine-48 polyubiquitination of proteins targeted for proteasomal degradation. To combat the accumulation of tau and proteasome impairment in the postsynaptic compartments of rTg4510 mouse brain, we stimulated the pituitary adenylate cyclase-activating polypeptide (PACAP) type 1 receptor (PAC1R) with its ligand PACAP administered intracerebroventricularly to rTg4510 mice. We observed enhanced synaptic proteasome activity and reduced total tau in postsynaptic compartments in mouse brain after PACAP treatment. The clearance of tau from postsynaptic compartments correlated with attenuated tauopathy and improved cognitive performance of rTg4510 transgenic mice on two behavioral tests. These results suggest that activating PAC1R could prevent accumulation of aggregate-prone tau and indicate a potential therapeutic approach for AD and other tauopathies.
We report the first measurements of anisotropy in the cosmic microwave background (CMB) radiation with the Arcminute Cosmology Bolometer Array Receiver (ACBAR). The instrument was installed on the ...2.1 m Viper telescope at the South Pole in 2001 January; the data presented here are the product of observations up to and including 2002 July. We present two deep differential maps produced by subtracting leading and trailing observations from the main field. The differential maps cover approximately 24 deg super(2) of sky selected for low dust contrast. These results represent the highest signal-to-noise ratio observations of CMB anisotropy to date; in the deepest 150 GHz band map, we reached an rms of approx8.0 mu K per 5arcmin beam. The 3 degree extent of the maps and small beam size of the experiment allow the measurement of the CMB anisotropy power spectrum over the range l = 150-3000 with resolution of delta l = 150. The contributions of galactic dust and radio sources to the observed anisotropy are negligible and are removed in the analysis. The resulting power spectrum is found to be consistent with the primary anisotropy expected in a concordance lambdaCDM universe.
Accumulation of tau in synapses in the early stages of Alzheimer's disease (AD) has been shown to cause synaptic damage, synaptic loss, and the spread of tau pathology through trans-synaptically ...connected neurons. Moreover, synaptic loss correlates with a decline in cognitive function, providing an opportunity to investigate therapeutic strategies to target synapses and synaptic tau to rescue or prevent cognitive decline in AD. One of the promising synaptic targets is the 5-HT4 serotonergic receptor present postsynaptically in the brain structures involved in the memory processes. 5-HT4R stimulation exerts synaptogenic and pro-cognitive effects involving synapse-to-nucleus signaling essential for synaptic plasticity. However, it is not known whether 5-HT4R activation has a therapeutic effect on tau pathology.
The goal of this study was to investigate the impact of chronic stimulation of 5-HT4R by two agonists, prucalopride and RS-67333, in PS19 mice, a model of tauopathy. We utilized gradient assays to isolate pre- and post-synaptic compartments, followed by biochemical analyses for tau species and ubiquitinated proteins in the synaptic compartments and total brain tissue. Next, we performed kinetic assays to test the proteasome's hydrolysis capacity in treatment conditions. Moreover, behavioral tests such as the open field and non-maternal nest-building tests were used to evaluate anxiety-like behaviors and hippocampal-related cognitive functioning in the treatment paradigm.
Our results show that 5-HT4R agonism reduced tauopathy, reduced synaptic tau, increased proteasome activity, and improved cognitive functioning in PS19 mice. Our data suggest that enhanced proteasome activity by synaptic mediated signaling leads to the enhanced turnover of tau initially within synapses where the receptors are localized, and over time, the treatment attenuated the accumulation of tau aggregation and improved cognitive functioning of the PS19 mice.
Therefore, stimulation of 5-HT4R offers a promising therapy to rescue synapses from the accumulation of toxic synaptic tau, evident in the early stages of AD.
Background:
The COVID-19 pandemic created an unprecedented residency application cycle that required the use of virtual interviews. The inaugural class of applicants participating in virtual ...interviews were surveyed concerning their preferences and suggestions for future application cycles.
Methods:
A survey was distributed to 349 individuals who applied for an integrated plastic surgery residency position at three institutions during the 2020–21 application cycle. Responses were analyzed to determine the most popular attributes of virtual interviews.
Results:
Response rate was 44%. Eighty-six percent of applicants valued having time to consider their interview offers before scheduling; however, nearly one-third felt the instructions provided by programs lacked clarity and did not abide by the American Council of Academic Plastic Surgeons guidelines. Eighty-two percent of applicants valued having a preinterview social, and most preferred smaller breakout rooms organized by themes. A short interview day (less than three hours) was associated with less applicant familiarity with the program, its people, and its location when compared with medium (three to seven hours) and long (more than seven hours) interview days (
P
< 0.001 for all). Eighty percent of applicants preferred an interview day where they were placed into interview rooms by a program coordinator.
Conclusions:
The virtual interview format can be optimized in many ways to benefit both applicants and programs. The data presented in this article provide suggestions for future iterations of virtual interviews.
Introduction:
Residency programs and applicants were forced to hold virtual interviews during the 2020–2021 application cycle. Inability to evaluate a program and/or applicant in person has ...intangible drawbacks. However, there are obvious advantages: cost, convenience, and comfort. Do the advantages outweigh the disadvantages? How have applicant behaviors changed to learn about programs in a virtual-only interview process?
Methods:
A survey was distributed to 302 applicants to a single plastic surgery residency program during the 2020 application cycle. Demographics, social media presence and utilization, and experience with the virtual application and interview process were analyzed. A 2018 survey from our institution was compared with a subset of questions for longitudinal analysis.
Results:
Seventy-six respondents (25.2%) completed the survey. Most applicants (88.2%) spent less than $1000 during the interview and application cycle. Over half (56.6%) did not receive letters of recommendation from outside their home program. A significant minority (27.6%) of applicants attended more than one interview in a single day. Compared to 2018, applicants in 2021 were significantly more likely to access alternative digital resources (forums/discussion boards, social media, and podcasts) when learning about programs. Average number of interviews remains in the range of pre-COVID studies, but the percentage of interviews attended increased.
Conclusions:
Applicants spent substantially less money on interviews and relied on alternative digital sources to learn about residency programs. This study objectively quantifies the advantages of virtual interviews. Disadvantages include inability to assess “fit” and lack of nonverbal communication.
Endoscopically assisted craniofacial surgery (EACS) has numerous advantages over traditional, open approaches, such as fronto-orbital advancement in treating nonsyndromic craniosynostosis. However, ...several articles report high reoperation rates in syndromic patients treated with EACS. This meta-analysis and review examines undesirable outcome rates (UORs), defined as reoperation or Whitaker category III/IV, in syndromic patients undergoing primary EACS compared with procedures that actively expand the cranial vault.
PubMed and Embase were searched in June 2022 to identify all articles reporting primary reoperation or Whitaker outcomes for syndromic patients undergoing cranial vault expanding surgery or suturectomy. A meta-analysis of proportions was performed comparing UORs, and a trim-and-fill adjustment method was used to validate sensitivity and assess publication bias.
A total of 721 articles were screened. Five EACS articles (83 patients) and 22 active approach articles (478 patients) met inclusion criteria. Average UORs for EACS and active approaches were 26% (14%-38%) and 20% (13%-28%), respectively (
= 0.18). Reoperation occurred earlier in EACS patients (13.7 months postprimary surgery versus 37.1 months for active approaches,
= 0.003). Relapse presentations and reason for reoperation were also reviewed. Subjectively, EACS UORs were higher in all syndromes except Apert, and Saethre-Chotzen patients had the highest UOR for both approaches.
There was no statistically significant increase in UORs among syndromic patients treated with EACS compared with traditional approaches, although EACS patients required revision significantly sooner. Uncertainties regarding the long-term efficacy of EACS in children with syndromic craniosynostosis should be revisited as more data become available.
Surgical management in those with moderate-to-severe airway obstruction includes tongue-lip adhesion, tracheostomy, and/or mandibular distraction osteogenesis. This article describes a transfacial ...two-pin external device technique for mandibular distraction osteogenesis, utilizing minimal dissection.
The first percutaneous pin is transcutaneously placed just inferior to the sigmoid notch parallel to the interpupillary line. The pin is then advanced through the pterygoid musculature at the base of the pterygoid plates, toward the contralateral ramus, and exits the skin. A second parallel pin is placed spanning the bilateral mandibular parasymphysis distal to the region of the future canine. With the pins in place, bilateral high ramus transverse corticotomies are performed. Using univector distractor devices, the length of activation varies, with the goal of overdistraction to achieve a class III relationship of the alveolar ridges. Consolidation is limited to a 1:1 period with the activation phase, and removal is performed by cutting and pulling the pins out of the face.
To guide optimal transcutaneous pin placement, transfacial pins were then placed through twenty segmented mandibles. Mean upper pin (UP) distance was 20.7 ± 1.1 mm from the tragus. The distance between the cutaneous entry of the UP and lower pin was 23.5 ± 0.9 mm, and the tragion-UP-lower pin angle was 118.7 ± 2.9°.
The two-pin technique has potential advantages regarding nerve injury and mandibular growth, given an intraoral approach with limited dissection. It may safely be performed on neonates whose small size may preclude the use of internal distractor devices.
BACKGROUND:Industry-printed (IP) 3-dimensional (3D) models are commonly used for secondary midfacial reconstructive cases but not for acute cases due to their high cost and long turnaround time. We ...have begun using in-house (IH) printed models for complex unilateral midface trauma. We hypothesized that IH models would decrease cost and turnaround time, compared with IP models.
METHODS:We retrospectively examined cost and turnaround time data from midface trauma cases performed in 2017–2019 using 3D models (total, n = 15; IH, n = 10; IP, n = 5). Data for IH models were obtained through itemized cost reports from our Biomedical Engineering Department, where the models were printed. Data associated with IP models were obtained through itemized cost reports from our industry vendor. Perioperative data were collected from electronic medical records.
RESULTS:The average cost for IH models ($236.38 ± 26.17) was significantly less (P < 0.001) than that for IP models ($1677.82 ± 488.43). Minimal possible time from planning to model delivery was determined. IH models could be produced in as little as 4.65 hours, whereas the IP models required a minimum of 5 days (120 hours) from order placement. There were no significant differences in average operating room time (P = 0.34), surgical complications, or subjective outcomes, but there was a significant difference in estimated blood loss (P = 0.04).
CONCLUSION:Utilization of IH 3D skull models is a creative and practical adjunct to complex unilateral midfacial trauma that also reduces cost and turnaround time compared with IP 3D models.
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