Citations

Background Long surgical procedures with loupe magnification and microscopes may put microsurgeons at an increased risk of musculoskeletal discomfort. Identifying the prevalence and impact of work-related musculoskeletal discomfort may guide preventive strategies to prolong well-being, job satisfaction, and career duration. Methods An online 29-question survey was designed to evaluate work-related musculoskeletal discomfort. The survey was created and distributed electronically through a private survey research center and was sent to the members of the American Society for Reconstructive Microsurgery. Results There were 117 respondents (16.7% response rate): 80% were men; 69% were aged 31 to 50 years; and 68% were in academic practice. On a scale of 0 to 10 (0, no pain and 10, worst pain), the median for work-related musculoskeletal discomfort for surgery without loupes or microscope was 2; with loupes, 4; and with a microscope, 5. Pain was most common in the neck. Half of the surgeons reported pain within 4 hours of surgery, and 57% feared that pain would influence future surgical performance. Surgeon discomfort affected posture (72%), stamina (36%), sleep (29%), relationships (25%), concentration (22%), and surgical speed (19%). Tremor caused by the discomfort occurred in 8%. Medical treatment for discomfort was sought by 29%. Time off work for treatment occurred for 8%. Conclusion Work-related musculoskeletal discomfort can affect many aspects of a microsurgeon's life and has the potential to limit a surgeon's ability to operate. Therefore, more emphasis is needed in the surgical community on the important issues of occupational health and surgical ergonomics for microsurgeons.

Abstract UNC-45A, a highly conserved member of the UCS (UNC45A/CRO1/SHE4P) protein family of cochaperones, plays an important role in regulating cytoskeletal-associated functions in invertebrates and mammalian cells, including cytokinesis, exocytosis, cell motility, and neuronal development. Here, for the first time, UNC-45A is demonstrated to function as a mitotic spindle-associated protein that destabilizes microtubules (MT) activity. Using in vitro biophysical reconstitution and total internal reflection fluorescence microscopy analysis, we reveal that UNC-45A directly binds to taxol-stabilized MTs in the absence of any additional cellular cofactors or other MT-associated proteins and acts as an ATP-independent MT destabilizer. In cells, UNC-45A binds to and destabilizes mitotic spindles, and its depletion causes severe defects in chromosome congression and segregation. UNC-45A is overexpressed in human clinical specimens from chemoresistant ovarian cancer and that UNC-45A–overexpressing cells resist chromosome missegregation and aneuploidy when treated with clinically relevant concentrations of paclitaxel. Lastly, UNC-45A depletion exacerbates paclitaxel-mediated stabilizing effects on mitotic spindles and restores sensitivity to paclitaxel. Implications: These findings reveal novel and significant roles for UNC-45A in regulation of cytoskeletal dynamics, broadening our understanding of the basic mechanisms regulating MT stability and human cancer susceptibility to paclitaxel, one of the most widely used chemotherapy agents for the treatment of human cancers.

Abstract Frequent detection of serous tubal intraepithelial carcinoma (STIC) among BRCA1/2 mutation carriers undergoing risk-reducing surgery prompted the hypothesis that many adnexal high-grade serous carcinomas (HGSCs) arise from the fallopian tube, rather than the ovary, as supposed. The changing paradigm has important implications for HGSC prevention. Most data related to the frequency of STIC are derived from case series and estimates vary widely. Therefore, we analyzed population-based data from 10 523 surgeries including salpingectomy (Jan 2014–Dec 2016) that were examined using the “Sectioning and Extensively Examining the Fimbria” protocol, which optimizes STIC detection. Overall, STIC was detected in 40 (0.38%) specimens, including 32 diagnosed with concurrent gynecologic cancer. STIC was detected in 8 (<0.01%) of 9392 cases with benign diagnoses. We conclude that the relative rarity of STIC diagnoses in routine pathology practice has critical implications for research aiming to elucidate the pathogenesis of HGSC and developing prevention strategies.

BackgroundGradient nonlinearity (GNL) leads to biased apparent diffusion coefficients (ADCs) in diffusion‐weighted imaging. A gradient nonlinearity correction (GNLC) method has been developed for whole body systems, but is yet to be tested for the new compact 3T (C3T) scanner, which exhibits more complex GNL due to its asymmetrical design.PurposeTo assess the improvement of ADC quantification with GNLC for the C3T scanner.Study TypePhantom measurements and retrospective analysis of patient data.Phantom/SubjectsA diffusion quality control phantom with vials containing 0–30% polyvinylpyrrolidone in water was used. For in vivo data, 12 patient exams were analyzed (median age, 33).Field Strength/SequenceImaging was performed on the C3T and two commercial 3T scanners. A clinical DWI (repetition time [TR] = 10,000 msec, echo time [TE] = minimum, b = 1000 s/mm2) sequence was used for phantom imaging and 10 patient cases and a clinical DTI (TR = 6000–10,000 msec, TE = minimum, b = 1000 s/mm2) sequence was used for two patient cases.AssessmentThe 0% vial was measured along three orthogonal axes, and at two different temperatures. The ADC for each concentration was compared between the C3T and two whole‐body scanners. Cerebrospinal fluid and white matter ADCs were quantified for each patient and compared to values in literature.Statistical TestsPaired t‐test and two‐way analysis of variance (ANOVA).ResultsFor all PVP concentrations, the corrected ADC was within 2.5% of the reference ADC. On average, the ADC of cerebrospinal fluid and white matter post‐GNLC were within 1% and 6%, respectively, of values reported in the literature and were significantly different from the uncorrected data (P < 0.05).Data ConclusionThis study demonstrated that GNL effects were more severe for the C3T due to the asymmetric gradient design, but our implementation of a GNLC compensated for these effects, resulting in ADC values that are in good agreement with values from the literature.Level of Evidence: 4Technical Efficacy: Stage 2J. Magn. Reson. Imaging 2018;48:1498–1507

AbstractCellular studies indicate that endocannabinoid type‐1 retrograde signaling plays a major role in synaptic plasticity. Disruption of these processes by delta‐9‐tetrahydrocannabinol (THC) could produce alterations either in structural and functional brain connectivity or in their association in cannabis (CB) users. Graph theoretic structural and functional networks were generated with diffusion tensor imaging and resting‐state functional imaging in 37 current CB users and 31 healthy non‐users. The primary outcome measures were coupling between structural and functional connectivity, global network characteristics, association between the coupling and network properties, and measures of rich‐club organization. Structural–functional (SC–FC) coupling was globally preserved showing a positive association in current CB users. However, the users had disrupted associations between SC–FC coupling and network topological characteristics, most perturbed for shorter connections implying region‐specific disruption by CB use. Rich‐club analysis revealed impaired SC–FC coupling in the hippocampus and caudate of users. This study provides evidence of the abnormal SC–FC association in CB users. The effect was predominant in shorter connections of the brain network, suggesting that the impact of CB use or predispositional factors may be most apparent in local interconnections. Notably, the hippocampus and caudate specifically showed aberrant structural and functional coupling. These structures have high CB1 receptor density and may also be associated with changes in learning and habit formation that occur with chronic cannabis use.

5062 Background: Inflammation has been linked to prostate cancer (PCa) progression which may be mediated by the transcription factor nuclear factor kappa B (NFκB). Using a bioinformatic screen focused on NFκB pathway activation in lethal PCa, we identified the tumor suppressor ZFP36 as a key node of the NFκB network. We also showed in vitro that ZFP36 expression was inversely associated with both NFκB-controlled gene levels and proliferation and sensitivity to enzalutamide. We examined the role of ZFP36 and PCa progression in patient cohorts. Methods: The association between low mRNA expression of ZFP36 (levels in the lower quartile) and lethal PCa (defined as metastatic disease or death) was assessed with logistic regression among men with localized PCa in two independent cohorts treated with radical prostatectomy (RP). The discovery cohort was RP samples from Health Professional Follow-up Study and Physicians Health Study and the validation cohort was RP samples from Cleveland Clinic, Mayo Clinic, Johns Hopkins and MSKCC. In a third cohort from Cornell University, ZFP36 expression levels were assessed in RP samples from patients with localized PCa and biopsies of metastatic castration resistant prostate cancer (mCRPC). Results: Table 1 shows men with localized PCa and lower quartile of tumor ZFP36 expression had a nearly 2-fold higher risk of lethal PCa after adjusting for known clinical and histological prognostic features (age, RP Gleason score, T-stage); an association confirmed in the validation cohort. ZFP36 gene expression was also significantly lower in mCRPC (n=53) compared with a localized RP cohort (n=68) (p-value <0.0001). Conclusions: In humans lower ZFP36 in RP specimens is associated with clinically significant risk of lethal PCa after treatment with curative intent and lower ZFP36levels are found in metastatic tissue. [Table: see text]