Virtual Surgical Planning in Subscapular System Free Flap Reconstruction of Midface Defects.

OBJECTIVES: Reconstruction of the midface has many inherent challenges, including orbital support, skull base reconstruction, optimizing midface projection, separation of the nasal cavity and dental rehabilitation. Subscapular system free flaps (SF) have sufficient bone stock to support complex reconstruction and the option of separate soft tissue components. This study analyzes the effect of virtual surgical planning (VSP) in SF for midface on subsite reconstruction, bone segment contact and anatomic position. MATERIALS AND METHODS: Retrospective cohort of patients with midface defects that underwent SF reconstruction at a single tertiary care institution. RESULTS: Nine cases with VSP were compared to fourteen cases without VSP. VSP was associated with a higher number of successfully reconstructed subunits (5.9 vs 4.2, 95% CI of mean difference 0.31-3.04, p = 0.018), a higher number of successful bony contact between segments (2.2 vs 1.4, 95% CI of mean difference 0.0-1.6, p = 0.050), and a higher percent of segments in anatomic position (100% vs 71%, 95% CI of mean difference 2-55%, p = 0.035). When postoperative bone position after VSP reconstruction was compared to preoperative scans, the difference in anteroposterior, vertical and lateral projection compared to the preoperative \u27ideal\u27 bone position was82% of measurements. There were no flap losses. CONCLUSION: VSP may augment SF reconstruction of the midface by allowing for improved subunit reconstruction, bony segment contact and anatomically correct bone segment positioning. VSP can be a useful adjunct for complex midface reconstruction and the benefits should be weighed against cost

Technical Report: Distributed Parallel Computing Using Windows Desktop Systems

See also: http://sbml.org/Main_PageLike many large institutions, Indiana University has thousands of desktop computers devoted primarily to running office productivity applications on the Windows operating system, tasks which are necessary but that do not use the computers’ full capacity. This is a resource worth pursuing. However, the individual desktop systems do not offer enough processing power for a long enough period of time to complete large scientific computing applications. Some form of distributed, parallel programming is required, to make them worth the chase. They must be instantly available to their primary users, so they are available only intermittently. This has been a serious stumbling block: currently available communications libraries for distributed computing do not support such a dynamic communications world well. This paper introduces Simple Message Broker Library (SMBL), which provides the flexibility needed to take advantage of such ephemeral resources

Mining Disaggregase Sequence Space to Safely Counter TDP-43, FUS, and α-Synuclein Proteotoxicity.

Hsp104 is an AAA+ protein disaggregase, which can be potentiated via diverse mutations in its autoregulatory middle domain (MD) to mitigate toxic misfolding of TDP-43, FUS, and α-synuclein implicated in fatal neurodegenerative disorders. Problematically, potentiated MD variants can exhibit off-target toxicity. Here, we mine disaggregase sequence space to safely enhance Hsp104 activity via single mutations in nucleotide-binding domain 1 (NBD1) or NBD2. Like MD variants, NBD variants counter TDP-43, FUS, and α-synuclein toxicity and exhibit elevated ATPase and disaggregase activity. Unlike MD variants, non-toxic NBD1 and NBD2 variants emerge that rescue TDP-43, FUS, and α-synuclein toxicity. Potentiating substitutions alter NBD1 residues that contact ATP, ATP-binding residues, or the MD. Mutating the NBD2 protomer interface can also safely ameliorate Hsp104. Thus, we disambiguate allosteric regulation of Hsp104 by several tunable structural contacts, which can be engineered to spawn enhanced therapeutic disaggregases with minimal off-target toxicity

Functionally distinct T-helper cell phenotypes predict resistance to different types of parasites in a wild mammal

The adaptive immune system is critical to an effective response to infection in vertebrates, with T-helper (Th) cells pivotal in orchestrating these responses. In natural populations where co-infections are the norm, different Th responses are likely to play an important role in maintaining host health and fitness, a relationship which remains poorly understood in wild animals. In this study, we characterised variation in functionally distinct Th responses in a wild population of Soay sheep by enumerating cells expressing Th-subset specific transcription factors and quantifying Th-associated cytokines. We tested the prediction that raised Th1 and Th2 responses should predict reduced apicomplexan and helminth parasite burdens, respectively. All measures of Th-associated cytokine production increased with age, while Th17- and regulatory Th-associated cytokine production increased more rapidly with age in males than females. Independent of age, sex, and each other, IL-4 and Gata3 negatively predicted gastro-intestinal nematode faecal egg count, while IFN-γ negatively predicted coccidian faecal oocyst count. Our results provide important support from outside the laboratory that Th1 and Th2 responses predict resistance to different kinds of parasites, and illustrate how harnessing specific reagents and tools from laboratory immunology will illuminate our understanding of host-parasite interactions in the wild

Human TorsinA can function in the yeast cytosol as a molecular chaperone

TorsinA (TorA) is an AAA+ ATPAse linked to dystonia type 1 (DYT1), a neurological disorder that leads to uncontrollable muscular movements. Although DYT1 is linked to a 3bp deletion in the C terminus of TorA, the biological function of TorA remains to be established. Here we use the yeast Saccharomyces cerevisiae as a tractable in vivo model to explore TorA function. We demonstrate that TorA can protect yeast cells against different forms of environmental stress and show that in the absence of the molecular disaggregase Hsp104, TorA can refold heat-denatured luciferase in vivo in an ATP-dependent manner. However, this activity requires TorA to be translocated to the cytoplasm from the ER in order to access and process cytoplasmic protein aggregates. Furthermore, mutational or chemical inactivation of the ATPase activity of TorA blocks this activity. We also find that TorA can inhibit the propagation of certain conformational variants of [ PSI +], the aggregated prion form of the endogenous Sup35 protein. Finally, we show that while cellular localisation remains unchanged in the dystonia-linked TorA mutant ?E302-303, the ability of this mutant form of TorA to protect against cellular stress and to facilitate protein refolding, is impaired, consistent with it being a loss of function mutation

The mediation of social influences on smoking cessation and awareness of the early signs of lung cancer

Background Whilst there has been no clear consensus on the potential for earlier diagnosis of lung cancer, recent research has suggested that the time between symptom onset and consultation can be long enough to plausibly affect prognosis. In this article, we present findings from a qualitative study involving in-depth interviews with patients who had been diagnosed with lung cancer (n = 11), and people who were at heightened risk of developing the disease (n = 14). Methods A grounded theory methodology was drawn upon to conduct thematic and narrative based approaches to analysis. Results The paper focuses on three main themes which emerged from the study: i) fatalism and resignation in pathways to help-seeking and the process of diagnosis; ii) Awareness of smoking risk and response to cessation information and advice. iii) The role of social and other networks on help-seeking. Key findings included: poor awareness among participants of the symptoms of lung cancer; ambivalence about the dangers of smoking; the perception of lung cancer as part of a homogenisation of multiple illnesses; close social networks as a key trigger in help-seeking. Conclusions We suggest that future smoking cessation and lung cancer awareness campaigns could usefully capitalise on the influence of close social networks, and would benefit from taking a ‘softer’ approach

Factors impacting successful salvage of the failing free flap

Background Understanding factors impacting successful salvage of a compromised free flap. Methods Multi-institutional review of free flap reconstructions for head and neck defects (n = 1764). Results Free flap compromise rate: 9% (n = 162); 46% salvaged (n = 74). Higher salvage rates in initial 48 hours (64%) vs after (30%; P \u3c .001). Greater compromise (14%) and failure (8%) if inset challenging vs straightforward (6% compromise, 4% failure; P = .035). Greater compromise (23%) and failure (17%) following intraoperative anastomosis revision vs no revision (7% compromise, 4% failure; P \u3c .0001). Success following arterial insufficiency was lower (60% failed, 40% salvaged) vs venous congestion (23% failed, 77% salvaged) (P \u3c .0001). Greater flap salvage following thrombectomy (66%) vs no thrombectomy (34%; P \u3c .0001). Greater flap salvage if operative duration ≤8 hours (57%), vs \u3e8 hours (40%) (P = .04). Conclusions There were higher rates of free flap salvage if the vascular compromise occurred within 48 hours, if due to venous congestion, if operative duration ≤8 hours, and if the anastomosis did not require intraoperative revision

Factors Associated with Free Flap Failures in Head and Neck Reconstruction

To investigate causes of failure of free flap reconstructions in patients undergoing reconstruction of head and neck defects. Case series with chart review. Single tertiary care center. Patients underwent reconstruction between January 2007 and June 2017 (n = 892). Variables included were clinical characteristics, social history, defect site, donor tissue, ischemia time, and postoperative complications. Statistical methods used include univariable and multivariable analysis of failure. The overall failure rate was 4.8% (n = 43). Intraoperative ischemia time was associated with free flap failures (odds ratio [OR], 1.062; 95% confidence interval [CI], 1.019-1.107; = .004) for each addition of 5 minutes. Free flaps that required pedicle revision at time of initial surgery were 9 times more likely to fail (OR, 9.953; 95% CI, 3.242-27.732; < .001). Patients who experienced alcohol withdrawal after free flap placement were 3.7 times more likely to experience flap failure (OR, 3.690; 95% CI, 1.141-10.330; = .031). Ischemia time remained an independent significant risk factor for failure in nonosteocutaneous free flaps (OR, 1.105; 95% CI, 1.031-1.185). Alcohol withdrawal was associated with free flap failure in osteocutaneous reconstructions (OR, 5.046; 95% CI 1.103-19.805) while hypertension was found to be protective (OR, 0.056; 95% CI, 0.000-0.445). Prolonged ischemia time, pedicle revision, and alcohol withdrawal were associated with higher rates of flap failure. Employing strategies to minimize ischemic time may have potential to decrease failure rates. Flaps that require pedicle revision and patients with a history of significant alcohol use require closer monitoring