Cutting Edge Developments in Spine Surgery at the University of Missouri.

The treatment of spinal pathologies has evolved significantly from the times of Hippocrates and Galen to the current era. This evolution has led to the development of cutting-edge technologies to improve surgical techniques and patient outcomes. The University of Missouri Health System is a high-volume, tertiary care academic medical center that serves a large catchment area in central Missouri and beyond. The Department of Neurosurgery has sought to integrate the best available technologies to serve their spine patients. These technological advancements include intra-operative image guidance, robotic spine surgery, minimally invasive techniques, motion preservation surgery, and interdisciplinary care of metastatic disease to the spine. These advances have resulted in safer surgeries with enhanced outcomes at the University of Missouri. This integration of innovation demonstrates our tireless commitment to ensuring excellence in the comprehensive care of a diverse range of patients with complex spinal pathologies.

Predictors of Postoperative Segmental and Overall Lumbar Lordosis in Minimally Invasive Transforaminal Lumbar Interbody Fusion: A Consecutive Case Series.

STUDY DESIGN: Retrospective Case-Series. OBJECTIVES: Due to heterogeneity in previous studies, the effect of MI-TLIF on postoperative segmental lordosis (SL) and lumbar lordosis (LL) remains unclear. Therefore, we aim to identify radiographic factors associated with lordosis after surgery in a homogenous series of MI-TLIF patients. METHODS: A single-center retrospective review identified consecutive patients who underwent single-level MI-TLIF for grade 1 degenerative spondylolisthesis from 2015-2020. All surgeries underwent unilateral facetectomies and a contralateral facet release with expandable interbody cages. PROs included the ODI and NRS-BP for low-back pain. Radiographic measures included SL, disc height, percent spondylolisthesis, cage positioning, LL, PI-LL mismatch, sacral-slope, and pelvic-tilt. Surgeries were considered "lordosing" if the change in postoperative SL was ≥ +4° and "kyphosing" if ≤ -4°. Predictors of change in SL/LL were evaluated using Pearson's correlation and multivariable regression. RESULTS: A total of 73 patients with an average follow-up of 22.5 (range 12-61) months were included. Patients experienced significant improvements in ODI (29% ± 22% improvement, P < .001) and NRS-BP (3.3 ± 3 point improvement, P < .001). There was a significant increase in mean SL (Δ3.43° ± 4.37°, P < .001) while LL (Δ0.17° ± 6.98°, P > .05) remained stable. Thirty-eight (52%) patients experienced lordosing MI-TLIFs, compared to 4 (5%) kyphosing and 31 (43%) neutral MI-TLIFs. A lower preoperative SL and more anterior cage placement were associated with the greatest improvement in SL (ß = -.45° P = .001, ß = 15.06° P < .001, respectively). CONCLUSIONS: In our series, the majority of patients experienced lordosing or neutral MI-TLIFs (n = 69, 95%). Preoperative radiographic alignment and anterior cage placement were significantly associated with target SL following MI-TLIF.

Adaptive responses of yeast strains tolerant to acidic pH, acetate, and supraoptimal temperature.

Ethanol fermentations can be prematurely halted as Saccharomyces cerevisiae faces adverse conditions, such as acidic pH, presence of acetic acid, and supraoptimal temperatures. The knowledge on yeast responses to these conditions is essential to endowing a tolerant phenotype to another strain by targeted genetic manipulation. In this study, physiological and whole-genome analyses were conducted to obtain insights on molecular responses which potentially render yeast tolerant towards thermoacidic conditions. To this end, we used thermotolerant TTY23, acid tolerant AT22, and thermo-acid tolerant TAT12 strains previously generated by adaptive laboratory evolution (ALE) experiments. The results showed an increase in thermoacidic profiles in the tolerant strains. The whole-genome sequence revealed the importance of genes related to: H+, iron, and glycerol transport (i.e., PMA1, FRE1/2, JEN1, VMA2, VCX1, KHA1, AQY3, and ATO2); transcriptional regulation of stress responses to drugs, reactive oxygen species and heat-shock (i.e., HSF1, SKN7, BAS1, HFI1, and WAR1); and adjustments of fermentative growth and stress responses by glucose signaling pathways (i.e., ACS1, GPA1/2, RAS2, IRA2, and REG1). At 30 °C and pH 5.5, more than a thousand differentially expressed genes (DEGs) were identified in each strain. The integration of results revealed that evolved strains adjust their intracellular pH by H+ and acetic acid transport, modify their metabolism and stress responses via glucose signaling pathways, control of cellular ATP pools by regulating translation and de novo synthesis of nucleotides, and direct the synthesis, folding and rescue of proteins throughout the heat-shock stress response. Moreover, the motifs analysis in mutated transcription factors suggested a significant association of SFP1, YRR1, BAS1, HFI1, HSF1, and SKN7 TFs with DEGs found in thermoacidic tolerant yeast strains. KEY POINTS: • All the evolved strains overexpressed the plasma membrane H+ -ATPase PMA1 at optimal conditions • Tolerant strain TAT12 mutated genes encoding weak acid and heat response TFs HSF1, SKN7, and WAR1 • TFs HSF1 and SKN7 likely controlled the transcription of metabolic genes associated to heat and acid tolerance.

Feasibility and Acceptability of a Preoperative Multimodal Mobile Health Assessment in Spine Surgery Candidates.

BACKGROUND: Rapid growth in smartphone use has expanded opportunities to use mobile health (mHealth) technology to collect real-time patient-reported and objective biometric data. These data may have important implication for personalized treatments of degenerative spine disease. However, no large-scale study has examined the feasibility and acceptability of these methods in spine surgery patients. OBJECTIVE: To evaluate the feasibility and acceptability of a multimodal preoperative mHealth assessment in patients with degenerative spine disease. METHODS: Adults undergoing elective spine surgery were provided with Fitbit trackers and sent preoperative ecological momentary assessments (EMAs) assessing pain, disability, mood, and catastrophizing 5 times daily for 3 weeks. Objective adherence rates and a subjective acceptability survey were used to evaluate feasibility of these methods. RESULTS: The 77 included participants completed an average of 82 EMAs each, with an average completion rate of 86%. Younger age and chronic pulmonary disease were significantly associated with lower EMA adherence. Seventy-two (93%) participants completed Fitbit monitoring and wore the Fitbits for an average of 247 hours each. On average, participants wore the Fitbits for at least 12 hours per day for 15 days. Only worse mood scores were independently associated with lower Fitbit adherence. Most participants endorsed positive experiences with the study protocol, including 91% who said they would be willing to complete EMAs to improve their preoperative surgical guidance. CONCLUSION: Spine fusion candidates successfully completed a preoperative multimodal mHealth assessment with high acceptability. The intensive longitudinal data collected may provide new insights that improve patient selection and treatment guidance.

Clinically meaningful improvement in disabilities of arm, shoulder, and hand (DASH) following cervical spine surgery.

BACKGROUND CONTEXT: Patients with cervical spine disease suffer from upper limb disability. At present, no clinical benchmarks exist for clinically meaningful change in the upper limb function following cervical spine surgery. PURPOSE: Primary: to establish clinically meaningful metrics; the minimal clinically important difference (MCID) and substantial clinical benefit (SCB) of upper limb functional improvement in patients following cervical spine surgery. Secondary: to identify the prognostic factors of MCID and SCB of upper limb function following cervical spine surgery. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: Adult patients ≥18 years of age who underwent cervical spine surgery from 2012 to 2016. OUTCOME MEASURES: Patient-reported outcomes: Neck disability index (NDI) and Disabilities of Arm, Shoulder, and Hand (DASH). METHODS: MCID was defined as minimal improvement and SCB as substantial improvement in the DASH score at last follow-up. The anchor-based methods (ROC analyses) defined optimal MCID and SCB thresholds with area under curve (AUC) in discriminating improved vs. non-improved patients. The MCID was also calculated by distribution-based methods: half standard-deviation (0.5-SD) and standard error of the mean (SEM) method. A multivariable logistic regression evaluated the impact of baseline factors in achieving the MCID and SCB in DASH following cervical spine surgery. RESULTS: Between 2012 and 2016, 1,046 patients with average age of 57±11.3 years, 53% males, underwent cervical spine surgery. Using the ROC analysis, the threshold for MCID was -8 points with AUC of 0.73 (95% CI: 0.67-0.79) and the SCB was -18 points with AUC of 0.88 (95% confidence interval [CI]: 0.85-0.91). The MCID was -11 points by 0.5-SD and -12 points by SEM-method. On multivariable analysis, patients with myelopathy had lower odds of achieving MCID and SCB, whereas older patients and those with ≥6 months duration of symptoms had lower odds of achieving DASH MCID and SCB respectively. CONCLUSIONS: In patients undergoing cervical spine surgery, MCID of -8 points and SCB of -18 points in DASH improvement may be considered clinically significant. These metrics may enable evaluation of minimal and substantial improvement in the upper extremity function following cervical spine surgery.

Ice plant root plasma membrane aquaporins are regulated by clathrin-coated vesicles in response to salt stress.

The regulation of root Plasma membrane (PM) Intrinsic Protein (PIP)-type aquaporins (AQPs) is potentially important for salinity tolerance. However, the molecular and cellular details underlying this process in halophytes remain unclear. Using free-flow electrophoresis and label-free proteomics, we report that the increased abundance of PIPs at the PM of the halophyte ice plant (Mesembryanthemum crystallinum L.) roots under salinity conditions is regulated by clathrin-coated vesicles (CCV). To understand this regulation, we analyzed several components of the M. crystallinum CCV complexes: clathrin light chain (McCLC) and subunits µ1 and µ2 of the adaptor protein (AP) complex (McAP1µ and McAP2µ). Co-localization analyses revealed the association between McPIP1;4 and McAP2µ and between McPIP2;1 and McAP1µ, observations corroborated by mbSUS assays, suggesting that AQP abundance at the PM is under the control of CCV. The ability of McPIP1;4 and McPIP2;1 to form homo- and hetero-oligomers was tested and confirmed, as well as their activity as water channels. Also, we found increased phosphorylation of McPIP2;1 only at the PM in response to salt stress. Our results indicate root PIPs from halophytes might be regulated through CCV trafficking and phosphorylation, impacting their localization, transport activity, and abundance under salinity conditions.

Association Between Neighborhood-Level Socioeconomic Disadvantage and Patient-Reported Outcomes in Lumbar Spine Surgery.

BACKGROUND: Despite an increased understanding of the impact of socioeconomic status on neurosurgical outcomes, the impact of neighborhood-level social determinants on lumbar spine surgery patient-reported outcomes remains unknown. OBJECTIVE: To evaluate the impact of geographic social deprivation on physical and mental health of lumbar surgery patients. METHODS: A single-center retrospective cohort study analyzing patients undergoing lumbar surgery for degenerative disease from 2015 to 2018 was performed. Surgeries were categorized as decompression only or decompression with fusion. The area deprivation index was used to define social deprivation. Study outcomes included preoperative and change in Patient-Reported Outcomes Measurement (PROMIS) physical function (PF), pain interference (PI), depression, and anxiety (mean follow-up: 43.3 weeks). Multivariable imputation was performed for missing data. One-way analysis of variance and multivariable linear regression were used to evaluate the association between area deprivation index and PROMIS scores. RESULTS: In our cohort of 2010 patients, those with the greatest social deprivation had significantly worse mean preoperative PROMIS scores compared with the least-deprived cohort (mean difference [95% CI]-PF: -2.5 [-3.7 to -1.4]; PI: 3.0 [2.0-4.1]; depression: 5.5 [3.4-7.5]; anxiety: 6.0 [3.8-8.2], all P < .001), without significant differences in change in these domains at latest follow-up (PF: +0.5 [-1.2 to 2.2]; PI: -0.2 [-1.7 to 2.1]; depression: -2 [-4.0 to 0.1]; anxiety: -2.6 [-4.9 to 0.4], all P > .05). CONCLUSION: Lumbar spine surgery patients with greater social deprivation present with worse preoperative physical and mental health but experience comparable benefit from surgery than patients with less deprivation, emphasizing the need to further understand social and health factors that may affect both disease severity and access to care.

Caracterización del tipo de sensibilidad dental de pacientes con periodontitis y su respuesta a los dentífricos / Characterization of the type of dental sensitivity of patients with periodontitis and their response to dentifrices

La hipersensibilidad de la dentina surge ante la exposición de esta y en respuesta a estímulos de diverso tipo, fundamentalmente de origen térmico, evaporativo, táctil, osmótico o químico. Se realizó una investigación abocada a caracterizar la hipersensibilidad dental de pacientes atendidos en consulta de odontología y la respuesta a determinado dentífrico utilizado. En el análisis de estimulación dental se tomaron 308 mediciones de la sensibilidad dental para todos los participantes (n=22), con 7 factores de tiempo (T0 antes del uso del producto, T3 días, T5 días, T8 días, T22 días y T29 días después del uso del dentífrico). Se realizó la prueba paramétrica regresión lineal simple para identificar la tendencia y el ajuste de los datos, al considerar dichas variables como una serie temporal. Se utilizaron 22 tratamientos. Casi el 91,0% expreso que el dentífrico había cumplido sus expectativas, fundamentalmente por la reducción de la hipersensibilidad a corto plazo, mientras que aproximadamente 91,0% de los casos afirmó que compraría el dentífrico (20 casos, IC 95%: 72,2% y 97,5%), respectivamente(AU)

Dentin hypersensitivity arises when exposed to it and in response to various types of stimuli, mainly of thermal, tactile evaporative, osmotic or chemical origin. An investigation was carried out aimed at characterizing the dental hypersensitivity of patients seen in the dental office and the response to a certain toothpaste used. In the dental stimulation analysis, 308 measurements of tooth sensitivity were taken for all participants (n = 22), with 7 time factors (T0 before use of the product, T3 days, T5 days, T8 days, T22 days and T29 days after using the toothpaste). The simple linear regression parametric test was performed to identify the trend and the fit of the data, considering these variables as a time series. 22 treatments were used. Almost 91.0% believed that the toothpaste had met their expectations, mainly due to the reduction in hypersensitivity in the short term, while approximately 91.0% of the cases stated that they would buy the toothpaste (20 cases, 95% CI: 72 , 2% and 97.5%), respectively(AU)

Comparison of local and regional radiographic outcomes in minimally invasive and open TLIF: a propensity score-matched cohort.

OBJECTIVE: Local and regional radiographic outcomes following minimally invasive (MI) transforaminal lumbar interbody fusion (TLIF) versus open TLIF remain unclear. The purpose of this study was to provide a comprehensive assessment of local and regional radiographic parameters following MI-TLIF and open TLIF. The authors hypothesized that open TLIF provides greater segmental and global lordosis correction than MI-TLIF. METHODS: A single-center retrospective cohort study of consecutive patients undergoing MI- or open TLIF for grade I degenerative spondylolisthesis was performed. One-to-one nearest-neighbor propensity score matching (PSM) was used to match patients who underwent open TLIF to those who underwent MI-TLIF. Sagittal segmental radiographic measures included segmental lordosis (SL), anterior disc height (ADH), posterior disc height (PDH), foraminal height (FH), percent spondylolisthesis, and cage position. Lumbopelvic radiographic parameters included overall lumbar lordosis (LL), pelvic incidence (PI)-lumbar lordosis (PI-LL) mismatch, sacral slope (SS), and pelvic tilt (PT). Change in segmental or overall lordosis after surgery was considered "lordosing" if the change was > 0° and "kyphosing" if it was ≤ 0°. Student t-tests or Wilcoxon rank-sum tests were used to compare outcomes between MI-TLIF and open-TLIF groups. RESULTS: A total of 267 patients were included in the study, 114 (43%) who underwent MI-TLIF and 153 (57%) who underwent open TLIF, with an average follow-up of 56.6 weeks (SD 23.5 weeks). After PSM, there were 75 patients in each group. At the latest follow-up both MI- and open-TLIF patients experienced significant improvements in assessment scores obtained with the Oswestry Disability Index (ODI) and the numeric rating scale for low-back pain (NRS-BP), without significant differences between groups (p > 0.05). Both MI- and open-TLIF patients experienced significant improvements in SL, ADH, and percent corrected spondylolisthesis compared to baseline (p < 0.001). However, the MI-TLIF group experienced significantly larger magnitudes of correction with respect to these metrics (ΔSL 4.14° ± 4.35° vs 1.15° ± 3.88°, p < 0.001; ΔADH 4.25 ± 3.68 vs 1.41 ± 3.77 mm, p < 0.001; percent corrected spondylolisthesis: -10.82% ± 6.47% vs -5.87% ± 8.32%, p < 0.001). In the MI-TLIF group, LL improved in 44% (0.3° ± 8.5°) of the cases, compared to 48% (0.9° ± 6.4°) of the cases in the open-TLIF group (p > 0.05). Stratification by operative technique (unilateral vs bilateral facetectomy) and by interbody device (static vs expandable) did not yield statistically significant differences (p > 0.05). CONCLUSIONS: Both MI- and open-TLIF patients experienced significant improvements in patient-reported outcome (PRO) measures and local radiographic parameters, with neutral effects on regional alignment. Surprisingly, in our cohort, change in SL was significantly greater in MI-TLIF patients, perhaps reflecting the effect of operative techniques, technological innovations, and the preservation of the posterior tension band. Taking these results together, no significant overall differences in LL between groups were demonstrated, which suggests that MI-TLIF is comparable to open approaches in providing radiographic correction after surgery. These findings suggest that alignment targets can be achieved by either MI- or open-TLIF approaches, highlighting the importance of surgeon attention to these variables.

Pharyngoesophageal Damage from Hardware Extrusion at an Average of 7.5 Years After Anterior Cervical Diskectomy and Fusion: A Case Series, Discussion of Risk Factors, and Guide for Management.

OBJECTIVE: We present a single-institution case series of patients who experienced pharyngoesophageal damage, specifically from extruded hardware occurring at an average of 7.5 years after anterior cervical diskectomy and fusion (ACDF). METHODS: A retrospective chart review was conducted of patients who had undergone ACDF with subsequent delayed pharyngoesophageal perforation or erosion from extruded hardware ≥1 year after surgery. A discussion of the literature surrounding this complication, including risk factors and management, is also presented. RESULTS: Nine patients were identified (average age 58 years, 66.7% male) among a total of 4122 ACDF patients (incidence: 0.22%). Average time to injury was 7.5 years. Indications for initial ACDF were degenerative cervical disease (n = 7), ankylosing spondylitis (n = 1), and cervical fracture (n = 1). Eight patients had prior multilevel ACDF spanning 2 (n = 4), 3 (n = 1), or 4 levels (n = 2). Fusion levels for prior ACDF included C5-C7 (n = 3), C3-C7 (n = 2), C4-C7 (n = 1), C4-C6 (n = 1), C2-C5 (n = 1), and C6-C7 (n = 1). Pharyngoesophageal injuries included esophageal perforation (n = 3), pharyngeal perforation (n = 2), esophageal erosion (n = 3), and pharyngoesophageal erosion (n = 1). In most (n = 6) cases, the cause of pharyngoesophageal damage was due to ≥1 extruded screws. Dysphagia (n = 8) was the most common presenting symptom. For perforations (n = 5), 2 repairs used a rotational flap to reinforce a primary closure; the other 3 cases were repaired via primary closure. CONCLUSIONS: Pharyngoesophageal damage caused by extruded hardware may occur several years after ACDF. These delayed complications are difficult to predict. Proper screw placement may be the most important factor for minimizing the chances of this potentially devastating complication, particularly with multilevel constructs.

Efectividad de sustancias químicas en el clareamiento y biopelícula dental aplicado en el consultorio y ambulatorio / Effectiveness of chemical substances in bleaching and dental biofilm applied in the office and outpatient

El blanqueamiento dental está considerado como pieza fundamental en el embellecimiento de los seres humanos, ya que permite la restauración de la "sonrisa perfecta". Este proceso en sí, es poco invasivo y juega como un gran papel como aliado en la restauración satisfactoria de la sonrisa y autoestima del paciente. Es un procedimiento que debe ser aplicado cuidadosamente para lograr los efectos positivos del mismo. El fundamento de esta técnica es aclarar la tonalidad que han sufrido los dientes por diversos factores: extrinsecos, intrínsecos y decoloraciones internas. Durante el procedimiento, es usual el uso de peróxido de hidrógeno (H2O2) en concentraciones que van del 10 al 32 % en volumen o el peróxido de carbamida, un compuesto conformado por peróxido de hidrógeno y urea concentraciones del 10 al 22 %. El uso de peróxido de hidrógeno se lleva a cabo fundamentalmente en los consultorios, mientras que el uso del peróxido de carbamida es un procedimiento doméstico. A pesar de los excelentes resultados que se obtiene al usar ambos blanqueadores, su uso puede ocasionar erosiones dentales y sensibilidad dentaria. El primer caso, puede llevar a la adherencia de bacterias cariogénicas como el Strepctococus mutans responsable de caries. Los resultados obtenidos, demostraron que el peróxido de hidrógeno es un agente más agresivo que el peróxido de carbamida, lo cual origina mayor sensibilidad dentaria y un mayor control bacteriano; en cambio el peróxido de carbamida fue mejor blanqueador y originó menor sensibilidad dental(AU)

Tooth whitening is considered a fundamental piece in the beautification of human beings, since it allows the restoration of the "perfect smile". This process itself is minimally invasive and plays a great role as an ally in the satisfactory restoration of the patient's smile and self-esteem. It is a procedure that must be carefully applied to achieve its positive effects. The basis of this technique is to clarify the shade that the teeth have suffered due to various factors: extrinsic, intrinsic and internal discoloration. During the procedure, the use of hydrogen peroxide (H2O2) in concentrations ranging from 10 to 32% by volume or carbamide peroxide, a compound made up of hydrogen peroxide and urea concentrations of 10 to 22%, is usual. The use of hydrogen peroxide is mainly carried out in offices, while the use of carbamide peroxide is a home procedure. Despite the excellent results obtained by using both whiteners, their use can cause dental erosion and tooth sensitivity. The first case can lead to the adherence of cariogenic bacteria such as Streptococcus mutans responsible for caries. The results obtained showed that hydrogen peroxide is a more aggressive agent than carbamide peroxide, which causes greater dental sensitivity and greater bacterial control; On the other hand, carbamide peroxide was a better whitener and caused less dental sensitivity(AU)

A differential subcellular localization of two copper transporters from the COPT family suggests distinct roles in copper homeostasis in Physcomitrium patens.

The moss Physcomitrium (Physcomitrella) patens is a bryophyte that provides genetic information about the adaptation to the life on land by early Embryophytes and is a reference organism for comparative evolutionary studies in plants. Copper is an essential micronutrient for every living organism, its transport across the plasma membrane is achieved by the copper transport protein family COPT/CTR. Two genes related to the COPT family were identified in Physcomitrella patens, PpaCOPT1 and PpaCOPT2. Homology modelling of both proteins showed the presence of three putative transmembrane domains (TMD) and the Mx3M motif, constituting a potential Cu + selectivity filter present in other members of this family. Functional characterization of PpaCOPT1 and PpaCOPT2 in the yeast mutant ctr1Δctr3Δ restored its growth on medium with non-fermentable carbon sources at micromolar Cu concentrations, providing support that these two moss proteins function as high affinity Cu + transporters. Localization of PpaCOPT1 and PpaCOPT2 in yeast cells was observed at the tonoplast and plasma membrane, respectively. The heterologous expression of PpaCOPT2 in tobacco epidermal cells co-localized with the plasma membrane marker. Finally, only PpaCOPT1 was expressed in seven-day old protonema and was influenced by extracellular copper levels. This evidence suggests different roles of PpaCOPT1 and PpaCOPT2 in copper homeostasis in Physcomitrella patens.

Endonasal Free Flap Reconstruction Combined With Draf Frontal Sinusotomy for Complex Cerebrospinal Fluid Leak: A Technical Report & Case Series.

BACKGROUND: Frontal sinus cranialization with closure via bifrontal pericranial flaps is the gold standard for separating the nasofrontal recess from the intracranial cavity for posterior table defects. Despite the high success rate, cerebrospinal fluid (CSF) leak may persist and is particularly challenging when vascularized reconstructive options from the bicoronal incision are exhausted. OBJECTIVE: To assess a novel endonasal technique using an adipofascial radial forearm free flap delivered to the frontal recess through a Draf sinusotomy to repair complex CSF leaks from the frontal sinus. METHODS: A retrospective review of 3 patients (all male; ages 42, 43, and 69 yr) with persistent CSF leak despite frontal sinus cranialization and repair with bifrontal pericranium was performed. Etiology of injury was traumatic in 2 patients and iatrogenic in 1 patient after anaplastic meningioma treatment. To create space for the flap and repair the nasofrontal ducts, endoscopic Draf III (Case 1, 3) or Draf IIb left frontal sinusotomy (Case 2) was performed. The forearm flap was harvested, passed through a Caldwell-Luc exposure, and placed within the Draf frontal sinustomy. The flap vessels were tunneled to the left neck and anastomosed to the facial vessels by the mandibular notch. RESULTS: Intraoperatively, the flaps were well-seated and provided a watertight seal. Postoperative hospital courses were uncomplicated. There were no new CSF leaks or flap necrosis at 12, 14, and 16 mo. CONCLUSION: Endoscopic endonasal free flap reconstruction through a Draf procedure is a novel viable option for persistent CSF leak after failed frontal sinus cranialization.

Evaluation of the Metastatic Spine Disease Multidisciplinary Working Group Algorithms as Part of a Multidisciplinary Spine Tumor Conference.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The Metastatic Spine Disease Multidisciplinary Working Group Algorithms are evidence and expert opinion-based strategies for utilizing radiation therapy, interventional radiology procedures, and surgery to treat 5 types of spine metastases: asymptomatic spinal metastases, uncomplicated spinal metastases, stable vertebral compression fractures (VCF), unstable VCF, and metastatic epidural spinal cord compression (MESCC). Evaluation of this set of algorithms in a clinical setting is lacking. The authors aimed to identify rate of treatment adherence to the Working Group Algorithms and, subsequently, update these algorithms based on actual patient management decisions made at a single-institution, multidisciplinary, spine tumor conference. METHODS: Patients with metastatic spine disease from primary non-hematologic malignancies discussed at an institutional spine tumor conference from 2013 to 2016 were evaluated. Rates of Working Group Algorithms adherence were calculated for each type of metastasis. Based on the reasons for algorithm nonadherence, and patient outcomes in such cases, updated Working Group Algorithms recommendations were proposed. RESULTS: In total, 154 eligible patients with 171 spine metastases were evaluated. Rates of algorithm adherence were as follows: asymptomatic (67%), uncomplicated (73%), stable VCF (20%), unstable VCF (32%), and MESCC (41%). The most common deviation from the Working Group Algorithms was surgery for MESCC despite poor prognostic factors, but this treatment strategy was supported based on median survival surpassing 6 months in these patients. CONCLUSIONS: Adherence to the Working Group Algorithm was lowest for MESCC and VCF patients, but many nonadherent treatments were supported by patient survival outcomes. We proposed updates to the Working Group Algorithm based on these findings.

Validation of the Disabilities of the Arm, Shoulder, and Hand in Patients Undergoing Cervical Spine Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate the performance and convergent validity of the disabilities of the arm, shoulder, and hand (DASH) in comparison with the visual analog scale (VAS) for pain, and neck disability index (NDI) in patients undergoing cervical spine surgery. SUMMARY OF BACKGROUND DATA: Neck-specific disability scales do not adequately assess concurrent upper extremity involvement in patients with cervical spine disorders. The DASH is a patient-reported outcomes (PRO) instrument designed to measure functional disability due to upper extremity conditions but has additionally been shown to perform well in patients with neck disorders. METHODS: We identified patients who underwent cervical spine surgery at our institution between 2013 and 2016. We collected demographic information, clinical characteristics, and PRO measures-DASH, VAS, NDI-preoperatively, as well as early and late postoperatively. We calculated descriptive statistics and changes from baseline in PROs. Correlation coefficients were used to quantify the association between PRO measures. The analysis was stratified by radiculopathy and myelopathy diagnoses. RESULTS: A total of 1046 patients (52.8% male) with PROs data at baseline were included in the analysis. The mean age at surgery ±â€ŠSD was 57.2 ±â€Š11.3 years, and postoperative follow-up duration 12.7 ±â€Š10.7 months. The most common surgical procedure was anterior cervical discectomy and fusion (71.1%). Patients experienced clinically meaningful postoperative improvements in all PRO measures. The DASH showed moderate positive correlations with VAS preoperatively (Spearman rho = 0.43), as well as early (rho = 0.48) and late postoperatively (rho = 0.60). DASH and NDI scores were strongly positively correlated across operative states (Preoperative rho = 0.74, Early Postoperative rho = 0.78, Late Postoperative rho = 0.82). Stratified analysis by preoperative diagnosis showed similar within-groups trends and pairwise correlations. However, radiculopathy patients experienced larger magnitude early and late change scores. CONCLUSION: The DASH is a valid and responsive PRO measure to evaluate disabling upper extremity involvement in patients undergoing cervical spine surgery. LEVEL OF EVIDENCE: 3.

Erv14 cargo receptor participates in regulation of plasma-membrane potential, intracellular pH and potassium homeostasis via its interaction with K+-specific transporters Trk1 and Tok1.

Cargo receptors in the endoplasmic reticulum (ER) recognize and help membrane and soluble proteins along the secretory pathway to reach their location and functional site. We characterized physiological properties of Saccharomyces cerevisiae strains lacking the ERV14 gene, which encodes a cargo receptor part of COPII-coated vesicles that cycles between the ER and Golgi membranes. The lack of Erv14 resulted in larger cell volume, plasma-membrane hyperpolarization, and intracellular pH decrease. Cells lacking ERV14 exhibited increased sensitivity to toxic cationic drugs and decreased ability to grow on low K+. We found no change in the localization of plasma membrane H+-ATPase Pma1, Na+, K+-ATPase Ena1 and K+ importer Trk2 or vacuolar K+-Cl- co-transporter Vhc1 in the absence of Erv14. However, Erv14 influenced the targeting of two K+-specific plasma-membrane transport systems, Tok1 (K+ channel) and Trk1 (K+ importer), that were retained in the ER in erv14Δ cells. The lack of Erv14 resulted in growth phenotypes related to a diminished amount of Trk1 and Tok1 proteins. We confirmed that Rb+ whole-cell uptake via Trk1 is not efficient in cells lacking Erv14. ScErv14 helped to target Trk1 homologues from other yeast species to the S. cerevisiae plasma membrane. The direct interaction between Erv14 and Tok1 or Trk1 was confirmed by co-immunoprecipitation and by a mating-based Split Ubiquitin System. In summary, our results identify Tok1 and Trk1 to be new cargoes for Erv14 and show this receptor to be an important player participating in the maintenance of several physiological parameters of yeast cells.

CORNICHON sorting and regulation of GLR channels underlie pollen tube Ca2+ homeostasis.

Compared to animals, evolution of plant calcium (Ca2+) physiology has led to a loss of proteins for influx and small ligand-operated control of cytosolic Ca2+, leaving many Ca2+ mechanisms unaccounted for. Here, we show a mechanism for sorting and activation of glutamate receptor-like channels (GLRs) by CORNICHON HOMOLOG (CNIH) proteins. Single mutants of pollen-expressed Arabidopsis thaliana GLRs (AtGLRs) showed growth and Ca2+ flux phenotypes expected for plasma membrane Ca2+ channels. However, higher-order mutants of AtGLR3.3 revealed phenotypes contradicting this assumption. These discrepancies could be explained by subcellular AtGLR localization, and we explored the implication of AtCNIHs in this sorting. We found that AtGLRs interact with AtCNIH pairs, yielding specific intracellular localizations. AtCNIHs further trigger AtGLR activity in mammalian cells without any ligand. These results reveal a regulatory mechanism underlying Ca2+ homeostasis by sorting and activation of AtGLRs by AtCNIHs.

Fractional anisotropy to quantify cervical spondylotic myelopathy severity.

BACKGROUND: A number of clinical tools exist for measuring the severity of cervical spondylotic myelopathy (CSM). Several studies have recently described the use of non-invasive imaging biomarkers to assess severity of disease. These imaging markers may provide an additional tool to measure disease progression and represent a surrogate marker of response to therapy. Correlating these imaging biomarkers with clinical quantitative measures is critical for accurate therapeutic stratification and quantification of axonal injury. METHODS: Fourteen patients and seven healthy control subjects were enrolled. Patients were classified as mildly (7) or moderately (7) impaired based on Modified Japanese Orthopedic Association Scale. All patients underwent diffusion tensor imaging (DTI) and diffusion basis spectrum imaging (DBSI) analyses. In addition to standard neurological examination, all participants underwent 30-m Walking Test, 9-hole Peg Test (9HPT), grip strength, key pinch, and vibration sensation thresholds in the index finger and great toe. Differences in assessment scores between controls, mild and moderate CSM patients were correlated with DTI and DBSI derived fractional anisotropy (FA). RESULTS: Clinically, 30-meter walking times were significantly longer in the moderately impaired group than in the control group. Maximum 9HPT times were significantly longer in both the mildly and moderately impaired groups as compared to normal controls. Scores on great toe vibration sensation thresholds were lower in the mildly impaired and moderately impaired groups as compared to controls. We found no clear evidence for any differences in minimum grip strength, minimum key pinch, or index finger vibration sensation thresholds. There were moderately strong associations between DTI and DBSI FA values and 30-meter walking times and 9HPT. CONCLUSIONS: The 30-m Walking Test and 9HPT were both moderately to strongly associated with DTI/DBSI FA values. FA may represent an additional measure to help differentiate and stratify patients with mild or moderate CSM.

Plant and yeast cornichon possess a conserved acidic motif required for correct targeting of plasma membrane cargos.

The export of membrane proteins along the secretory pathway is initiated at the endoplasmic reticulum after proteins are folded and packaged inside this organelle by their recruiting into the coat complex COPII vesicles. It is proposed that cargo receptors are required for the correct transport of proteins to its target membrane, however, little is known about ER export signals for cargo receptors. Erv14/Cornichon belong to a well conserved protein family in Eukaryotes, and have been proposed to function as cargo receptors for many transmembrane proteins. Amino acid sequence alignment showed the presence of a conserved acidic motif in the C-terminal in homologues from plants and yeast. Here, we demonstrate that mutation of the C-terminal acidic motif from ScErv14 or OsCNIH1, did not alter the localization of these cargo receptors, however it modified the proper targeting of the plasma membrane transporters Nha1p, Pdr12p and Qdr2p. Our results suggest that mistargeting of these plasma membrane proteins is a consequence of a weaker interaction between the cargo receptor and cargo proteins caused by the mutation of the C-terminal acidic motif.