Characterization of Pik1 function in fission yeast reveals its conserved role in lipid synthesis and not cytokinesis.

Phosphatidylinositol (PI)-4-phosphate (PI4P) is a lipid found at the plasma membrane (PM) and Golgi in cells from yeast to humans. PI4P is generated from PI by PI4-kinases and can be converted into PI-4,5-bisphosphate [PI(4,5)P2]. Schizosaccharomyces pombe have two essential PI4-kinases - Stt4 and Pik1. Stt4 localizes to the PM, and its loss from the PM results in a decrease of PM PI4P and PI(4,5)P2. As a result, cells divide non-medially due to disrupted cytokinetic ring-PM anchoring. However, the localization and function of S. pombe Pik1 has not been thoroughly examined. Here, we found that Pik1 localizes exclusively to the trans-Golgi and is required for Golgi PI4P production. We determined that Ncs1 regulates Pik1, but unlike in other organisms, it is not required for Pik1 Golgi localization. When Pik1 function was disrupted, PM PI4P but not PI(4,5)P2 levels were reduced, a major difference compared with Stt4. We conclude that Stt4 is the chief enzyme responsible for producing the PI4P that generates PI(4,5)P2. Also, that cells with disrupted Pik1 do not divide asymmetrically highlights the specific importance of PM PI(4,5)P2 for cytokinetic ring-PM anchoring.

Characterization of Pik1 function in fission yeast reveals its conserved role in lipid synthesis and not cytokinesis.

Phosphatidylinositol (PI)-4-phosphate (PI4P) is a lipid found at the plasma membrane (PM) and Golgi in cells from yeast to humans. PI4P is generated from PI by PI4-kinases and can be converted to PI-4,5-bisphosphate [PI(4,5)P 2 ]. Schizosaccharomyces pombe have 2 essential PI4-kinases: Stt4 and Pik1. Stt4 localizes to the PM and its loss from the PM results in a decrease of PM PI4P and PI(4,5)P 2 . As a result, cells divide non-medially due to disrupted cytokinetic ring-PM anchoring. However, the localization and function of S. pombe Pik1 has not been thoroughly examined. Here, we found that Pik1 localizes exclusively to the trans-Golgi and is required for Golgi PI4P production. We determined that Ncs1 regulates Pik1, but unlike in other organisms, it is not required for Pik1 Golgi localization. When Pik1 function was disrupted, PM PI4P but not PI(4,5)P 2 levels were reduced, a major difference with Stt4. We conclude that Stt4 is the chief enzyme responsible for producing the PI4P that generates PI(4,5)P 2 . Also, that cells with disrupted Pik1 do not divide asymmetrically highlights the specific importance of PM PI(4,5)P 2 for cytokinetic ring-PM anchoring. Summary statement: Fission yeast Pik1 localizes exclusively to the trans-Golgi independently of Ncs1, where it contributes to PI4P but not PI(4,5)P 2 synthesis. Pik1 does not affect cytokinesis.

Incidence of Dysphonia and Dysphagia Exceeds Recurrent Laryngeal Nerve Injury During Thyroid Surgery.

OBJECTIVES: To determine the prevalence of separate and combined voice and swallowing impairments before and after total thyroidectomy and to delineate risk factors for these symptoms. METHODS: Retrospective review of 592 consecutive patients who underwent total thyroidectomy from July 2003 to August 2015. RESULTS: Combined voice and swallowing problems occurred preoperatively in 4.7% (11/234), 3.3% (3/92), and 6.0% (16/266) of patients with malignancy, hyperthyroidism, and benign euthyroid disease, respectively. Postoperatively, prevalence was 5.1%, 2.2%, and 1.9%, respectively. Benign euthyroid disease (20.7%) had the greatest risk of preoperative dysphagia (P = 0.003) and the largest glands (P < 0.001). Comparing before and after surgery, the cancer and benign euthyroid groups had decreased dysphagia (cancer: 11.5% vs. 6.0%, P = 0.034; benign: 20.7% vs. 3.8%, P < 0.001) but increased dysphonia (cancer: 19.2% vs. 28.6%, P = 0.017; benign: 15.8% vs. 27.1%, P = 0.002). Overall, 23/592 (3.9%) developed new dysphagia and 122/592 (20.6%) developed new dysphonia after surgery. Intraoperative recurrent laryngeal nerve transection occurred in 12 cases (2.0%). CONCLUSIONS: Total thyroidectomy resolved dysphagia but increased dysphonia in benign and malignant euthyroid patients. Voice and swallowing problems following thyroidectomy occurred more frequently than intraoperative recurrent laryngeal nerve transection, confirming symptoms often occur in the absence of suspected nerve injury.

Outcomes of Early Versus Delayed Completion Thyroidectomy for Malignancy.

PURPOSE: To determine whether time interval between hemi-thyroidectomy and subsequent completion thyroidectomy impacts outcomes. METHODS: Retrospective review of 68 patients having completion thyroidectomy from August 2012 to December 2019. Patients were separated into two groups based on the time interval between surgeries: early (≤10 days) or delayed (≥90 days). RESULTS: Patients who underwent delayed completion thyroidectomy (n = 17) had significantly higher rates of hypocalcemia and/or hypoparathyroidism (P = .03) and higher rates of requiring postoperative hospitalization (P=.07) compared to those who underwent early completion thyroidectomy (n = 51). Delayed completion had significantly lower risk of developing one or more of dysphonia, dysphagia, or vocal cord paresis postoperatively (P=.02). No patients developed hematoma or wound infection. CONCLUSIONS: Delayed completion thyroidectomy is associated with increased rates of hypocalcemia, but lower rates of dysphonia and dysphagia. Given the low risk of long-term complications in both groups, it may be beneficial to perform completion thyroidectomy early in order to expedite cancer treatment.

Total thyroidectomy: Safe and curative treatment option for hyperthyroidism.

BACKGROUND: While use of total thyroidectomy has increased in management of hyperthyroidism, concerns exist about increased surgical complication rates; most notably, hematoma, recurrent laryngeal nerve (RLN) injury, and hypocalcemia. METHODS: Retrospective cohort study of 454 patients undergoing total thyroidectomy between 2003 and 2015. All patients had surgery for hyperthyroidism, benign euthyroid disease, or thyroid malignancy. RESULTS: Total thyroidectomy for hyperthyroidism was not associated with an increased risk for any postoperative complication. Transient hypocalcemia, temporary dysphonia, and postoperative hematoma rates were not significantly different for patients with hyperthyroid (n = 91), euthyroid benign (n = 237), and malignant (n = 126) disease. Permanent hypocalcemia and recurrent laryngeal nerve injury were not noted in any hyperthyroid patients. Complication rates were similar for hyperthyroid patients with Graves' disease vs toxic multinodular goiter. CONCLUSION: This study affirms safety and efficacy of total thyroidectomy as standard treatment for hyperthyroidism.

Non-invasive tracking of disease progression in young dystrophic muscles using multi-parametric MRI at 14T.

In this study, multi-parametric magnetic resonance imaging (MRI) was conducted to monitor skeletal muscle changes in dystrophic (mdx4cv) and age-matched control (C57BL/6J) mice starting at 3 weeks of age. The objective of this study was to evaluate and characterize changes in muscle tissue characteristics of hind limbs in young, dystrophic mice using MRI. Mdx4cv (n = 25) and age-matched C57BL/6J (n = 5) were imaged at 3, 5, 7, 9, and 11 weeks of age. Multiple MR measurements were taken from the tibialis anterior, gastrocnemius, and soleus muscles. There were significant differences between dystrophic and control groups for all three muscle types when comparing transverse relaxation times (T2) in lower hind limb muscles. Additionally, fractional anisotropy, radial diffusivity, and eigenvalue analysis of diffusion tensor imaging also demonstrated significant differences between groups. Longitudinal relaxation times (T1) displayed no significant differences between groups. The earliest time points in the magnetization transfer ratio measurements displayed a significant difference. Histological analysis revealed significant differences in the tibialis anterior and gastrocnemius muscles between groups with the mdx mice displaying greater variability in muscle fiber size in later time points. The multi-parametric MRI approach offers a promising alternative for future development of a noninvasive avenue for tracking both disease progression and treatment response.

Tracheal Chondrosarcoma: Systematic Review of Tumor Characteristics, Diagnosis, and Treatment Outcomes with Case Report.

To our knowledge this is the first systematic review of tracheal chondrosarcoma treatment outcomes. Management insights are thoroughly discussed. Men constitute 93.8% of cases, and most of these occur in the distal trachea. The most common symptom, dyspnea, occurs in virtually all patients. Extratracheal extension had occurred in 78.6% of patients. Definitive treatment with tracheal resection showed no recurrences in 10 patients with mean follow-up of 3.1 years. Adjuvant radiotherapy may be utilized for improving local control when open complete resection cannot be performed, but only after endoscopic excision of gross tumor.

Detection and Evaluation of Renal Injury in Burst Wave Lithotripsy Using Ultrasound and Magnetic Resonance Imaging.

PURPOSE: Burst wave lithotripsy (BWL) is a transcutaneous technique with potential to safely and effectively fragment renal stones. Preclinical investigations of BWL require the assessment of potential renal injury. This study evaluates the capabilities of real-time ultrasound and MRI to detect and evaluate BWL injury that was induced in porcine kidneys. MATERIALS AND METHODS: Ten kidneys from five female farm pigs were treated with either a 170 or 335 kHz BWL transducer using variable treatment parameters and monitored in real-time with ultrasound. Eight kidneys were perfusion fixed and scanned with a 3-Tesla MRI scanner (T1-weighted, T2-weighted, and susceptibility-weighted imaging), followed by processing via an established histomorphometric technique for injury quantification. In addition, two kidneys were separately evaluated for histologic characterization of injury quality. RESULTS: Observed B-mode hyperechoes on ultrasound consistent with cavitation predicted the presence of BWL-induced renal injury with a sensitivity and specificity of 100% in comparison to the histomorphometric technique. Similarly, MRI detected renal injury with a sensitivity of 90% and specificity of 100% and was able to identify the scale of lesion volumes. The injuries purposefully generated with BWL were histologically similar to those formed by shock wave lithotripsy. CONCLUSIONS: BWL-induced renal injury can be detected with a high degree of sensitivity and specificity by real-time ultrasound and post-treatment ex vivo MRI. No injury occurred in this study without cavitation detected on ultrasound. Such capabilities for injury detection and lesion volume quantification on MRI can be used for preclinical testing of BWL.

Where to position osteotomies in genioglossal advancement surgery based on locations of the mental foramen, canine, lateral incisor, central incisor, and genial tubercle.

PURPOSE: The study aimed to provide precise measurements of anterior mandibular structural anatomy and to explore potential osteotomies for genioglossal advancement. METHODS: Cone beam computed tomography was used to analyze 33 randomly selected patients undergoing surgery for obstructive sleep apnea (OSA) between 2014 and 2016 at an academic surgical hospital. The locations of relevant mandibular structures were measured and statistical modeling was performed. RESULTS: Mean horizontal distances from midline to the mental foramina and the roots of the canine, lateral incisor, and central incisor were 22.11 ± 1.92, 13.56 ± 3.01, 6.19 ± 1.58, and 2.04 ± 0.87 mm, respectively. Mean vertical distances from the inferior border of the mandible were 15.15 ± 1.77, 17.11 ± 3.28, 20.48 ± 3.10, and 21.81 ± 3.49 mm, respectively. The superior border of the genial tubercle was 15.63 ± 2.75 mm, and the inferior border was 6.87 ± 3.29, from the inferior border of the mandible. The angle of decline of the best-fit line through the important structures was about 18° from the occlusion plane at the midline. CONCLUSIONS: A straight line estimating the mental foramen, canine, lateral incisor, and central incisor tooth roots crosses at a mean of 22.3-22.6 mm above the inferior border of the mandible at the midline and has an angle of decline of about 18°. Potential osteotomies made parallel to and below this line result in tradeoffs between maximizing capture of the genioglossus muscle attachment and risk of dental/neurovascular injury.

Effect of genioglossus, geniohyoid, and digastric advancement on tongue base and hyoid position.

OBJECTIVES/HYPOTHESIS: To assess the effect of genioglossus, geniohyoid, and anterior digastric muscle advancement on base of tongue and hyoid position. STUDY DESIGN: Cadaver experiments. METHODS: In fresh cadavers, the mandibular attachments of the genioglossus, geniohyoid, and anterior digastric muscles were advanced anteriorly by 6, 10, or 14 mm, and the anterior displacement of the base of tongue and hyoid was measured. The degrees of displacement of the tongue base and hyoid by the individual muscles and combinations of muscles were compared to one another. RESULTS: In 11 cadavers, 462 measurements were taken. Genioglossus advancement alone produced significantly greater tongue base advancement than any other muscle (P < .001). No combination of muscles produced significantly more tongue base advancement than the genioglossus alone. Geniohyoid (P < .001) and anterior digastric muscle (P < .001) advancement both produced significantly greater hyoid advancement than the genioglossus, but there was no difference between the two (p = .615). No combination of muscles produced significantly more hyoid advancement than the geniohyoid or anterior digastric alone. CONCLUSIONS: Genioglossus muscle advancement produces the greatest base of tongue advancement. Geniohyoid or anterior digastric muscle advancement produces the greatest hyoid advancement. Advancement of neither base of tongue nor hyoid was superior when combinations of muscles were moved. LEVEL OF EVIDENCE: NA Laryngoscope, 127:1938-1942, 2017.