The diagnostic role of T wave morphology biomarkers in congenital and acquired long QT syndrome: A systematic review.

INTRODUCTION: QTc prolongation is key in diagnosing long QT syndrome (LQTS), however 25%-50% with congenital LQTS (cLQTS) demonstrate a normal resting QTc. T wave morphology (TWM) can distinguish cLQTS subtypes but its role in acquired LQTS (aLQTS) is unclear. METHODS: Electronic databases were searched using the terms "LQTS," "long QT syndrome," "QTc prolongation," "prolonged QT," and "T wave," "T wave morphology," "T wave pattern," "T wave biomarkers." Whole text articles assessing TWM, independent of QTc, were included. RESULTS: Seventeen studies met criteria. TWM measurements included T-wave amplitude, duration, magnitude, Tpeak-Tend, QTpeak, left and right slope, center of gravity (COG), sigmoidal and polynomial classifiers, repolarizing integral, morphology combination score (MCS) and principal component analysis (PCA); and vectorcardiographic biomarkers. cLQTS were distinguished from controls by sigmoidal and polynomial classifiers, MCS, QTpeak, Tpeak-Tend, left slope; and COG x axis. MCS detected aLQTS more significantly than QTc. Flatness, asymmetry and notching, J-Tpeak; and Tpeak-Tend correlated with QTc in aLQTS. Multichannel block in aLQTS was identified by early repolarization (ERD30% ) and late repolarization (LRD30% ), with ERD reflecting hERG-specific blockade. Cardiac events were predicted in cLQTS by T wave flatness, notching, and inversion in leads II and V5 , left slope in lead V6 ; and COG last 25% in lead I. T wave right slope in lead I and T-roundness achieved this in aLQTS. CONCLUSION: Numerous TWM biomarkers which supplement QTc assessment were identified. Their diagnostic capabilities include differentiation of genotypes, identification of concealed LQTS, differentiating aLQTS from cLQTS; and determining multichannel versus hERG channel blockade.

Evaluating the role of graft integrity on outcomes: clinical and imaging results following superior capsular reconstruction.

BACKGROUND: Superior capsular reconstruction (SCR) addresses massive, irreparable rotator cuff tears in young patients. The purpose of this study was to retrospectively evaluate clinical outcomes and graft integrity in patients following SCR. METHODS: Thirty-four consecutive patients undergoing SCR by 2 surgeons with minimum 2-year follow-up were identified. Functional outcomes were obtained, including Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), visual analog scale (VAS), and Single Assessment Numeric Evaluation (SANE) scores. Graft integrity was evaluated on magnetic resonance images (MRIs). RESULTS: Thirty-five shoulders in 34 patients were identified. Four patients underwent subsequent surgery. The mean preoperative scores were SST 21.6 ± 17.6, ASES 28.3 ± 10.1, SANE 50.6 ± 22.1, and VAS 6.6 ± 1.7. The mean postoperative outcomes were SST 79.1 ± 19.6, ASES 79.9 ± 17.4, SANE 74.3 ± 18.7, and VAS 1.5 ± 2.2. There was statistically significant improvement in SST, ASES, and VAS following SCR. MRI revealed graft failure in 62% (n = 13 of 21) of shoulders. Radiographic evidence of graft healing did not have any effect on SST, ASES, SANE, or VAS scores. CONCLUSION: Given the high rate of graft failure without a significant difference in clinical outcomes, graft healing after SCR might not be an independent predictor of success. The improved clinical improvement in patients undergoing SCR may be due to other known beneficial aspects of the procedure, including partial rotator cuff repair, débridement, and biceps management.

Cell Wall Composition and Candidate Biosynthesis Gene Expression During Rice Development.

Cell walls of grasses, including cereal crops and biofuel grasses, comprise the majority of plant biomass and intimately influence plant growth, development and physiology. However, the functions of many cell wall synthesis genes, and the relationships among and the functions of cell wall components remain obscure. To better understand the patterns of cell wall accumulation and identify genes that act in grass cell wall biosynthesis, we characterized 30 samples from aerial organs of rice (Oryza sativa cv. Kitaake) at 10 developmental time points, 3-100 d post-germination. Within these samples, we measured 15 cell wall chemical components, enzymatic digestibility and 18 cell wall polysaccharide epitopes/ligands. We also used quantitative reverse transcription-PCR to measure expression of 50 glycosyltransferases, 15 acyltransferases and eight phenylpropanoid genes, many of which had previously been identified as being highly expressed in rice. Most cell wall components vary significantly during development, and correlations among them support current understanding of cell walls. We identified 92 significant correlations between cell wall components and gene expression and establish nine strong hypotheses for genes that synthesize xylans, mixed linkage glucan and pectin components. This work provides an extensive analysis of cell wall composition throughout rice development, identifies genes likely to synthesize grass cell walls, and provides a framework for development of genetically improved grasses for use in lignocellulosic biofuel production and agriculture.

Overexpression of a BAHD acyltransferase, OsAt10, alters rice cell wall hydroxycinnamic acid content and saccharification.

Grass cell wall properties influence food, feed, and biofuel feedstock usage efficiency. The glucuronoarabinoxylan of grass cell walls is esterified with the phenylpropanoid-derived hydroxycinnamic acids ferulic acid (FA) and para-coumaric acid (p-CA). Feruloyl esters undergo oxidative coupling with neighboring phenylpropanoids on glucuronoarabinoxylan and lignin. Examination of rice (Oryza sativa) mutants in a grass-expanded and -diverged clade of BAHD acyl-coenzyme A-utilizing transferases identified four mutants with altered cell wall FA or p-CA contents. Here, we report on the effects of overexpressing one of these genes, OsAt10 (LOC_Os06g39390), in rice. An activation-tagged line, OsAT10-D1, shows a 60% reduction in matrix polysaccharide-bound FA and an approximately 300% increase in p-CA in young leaf tissue but no discernible phenotypic alterations in vegetative development, lignin content, or lignin composition. Two additional independent OsAt10 overexpression lines show similar changes in FA and p-CA content. Cell wall fractionation and liquid chromatography-mass spectrometry experiments isolate the cell wall alterations in the mutant to ester conjugates of a five-carbon sugar with p-CA and FA. These results suggest that OsAT10 is a p-coumaroyl coenzyme A transferase involved in glucuronoarabinoxylan modification. Biomass from OsAT10-D1 exhibits a 20% to 40% increase in saccharification yield depending on the assay. Thus, OsAt10 is an attractive target for improving grass cell wall quality for fuel and animal feed.

Morbidity and Mortality After Burr Hole Craniostomy Versus Craniotomy for Chronic Subdural Hematoma Evacuation: A Single-Center Experience.

BACKGROUND: Chronic subdural hematomas (cSDHs) are common neurosurgical pathological entities and typically occur after trauma in elderly patients. The 2 most commonly used strategies for treatment have included burr hole drainage and craniotomy with decompression. However, the choice of these procedures has remained controversial and has been primarily determined by surgeon preference. We designed a matched-cohort analysis to compare these 2 procedures and identify the risk factors associated with the postoperative outcomes. Thus, we compared the rates of reoperation and mortality for patients who had undergone craniotomy versus burr hole evacuation for cSDH. METHODS: A retrospective review examining the data from 299 consecutive patients with cSHDs from 2002 to 2015 was performed. We compared the following endpoints between the 2 procedures: 30-day mortality, discharge to a skilled nursing facility, and the need for reoperation. We also compared the potential risk factors in the patients with different primary outcomes. RESULTS: Patients undergoing craniotomy had a decreased need for reoperation compared with patients treated with burr hole evacuation (7.5% vs. 15.7%; P = 0.044). Older age was associated with both increased disposition to a nursing facility and increased 30-day mortality in both groups. Increased 30-day mortality was associated with aspirin usage in patients who had undergone craniotomy and with warfarin (Coumadin) in patients who had undergone burr hole evacuation. CONCLUSIONS: Our study identified an increased need for reoperation for patients treated with burr hole evacuation compared with those undergoing craniotomy. Older age and low Glasgow coma scale scores were associated with worse outcomes in both groups. Certain methods of anticoagulation were also associated with worse outcomes, which varied between the 2 groups. We recommend that surgeons individualize the choice of procedure according to the specific patient characteristics with consideration of these findings.

Self-referrals versus physician referrals: What new patient visit yields an actual surgical case?

OBJECTIVE Spine surgeons in the United States continue to be overwhelmed by an aging population, and patients are waiting weeks to months for appointments. With a finite number of clinic visits per surgeon, analysis of referral sources needs to be explored. In this study, the authors evaluated patient referrals and their yield for surgical volume at a tertiary care center. METHODS This is a retrospective study of new patient visits by the spine surgery group at the Cleveland Clinic Center for Spine Health from 2011 to 2016. Data on all new or consultation visits for 5 identified spinal surgeons at the Center for Spine Health were collected. Patients with an identifiable referral source and who were at least 18 years of age at initial visit were included in this study. Univariate analysis was used to identify demographic differences among referral groups, and then multivariate analysis was used to evaluate those referral groups as significant predictors of surgical yield. RESULTS After adjusting for demographic differences across all referrals, multivariate analysis identified physician referrals as more likely (OR 1.48, 95% CI 1.04-2.10, p = 0.0293) to yield a surgical case than self-referrals. General practitioner referrals (OR 0.5616, 95% CI 0.3809-0.8278, p = 0.0036) were identified as less likely to yield surgical cases than referrals from interventionalists (OR 1.5296, p = 0.058) or neurologists (OR 1.7498, 95% CI 1.0057-3.0446, p = 0.0477). Additionally, 2 demographic factors, including distance from home and age, were identified as predictors of surgery. Local patients (OR 1.21, 95% CI 1.13-1.29, p = 0.018) and those 65 years of age or older (OR 0.80, 95% CI 0.72-0.87, p = 0.0023) were both more likely to need surgery after establishing care with a spine surgeon. CONCLUSIONS In conclusion, referrals from general practitioners and self-referrals are important areas where focused triaging may be necessary. Further research into midlevel providers and nonsurgical spine provider's role in these referrals for spine pathology is needed. Patients from outside of the state or younger than 65 years could benefit from pre-visit screening as well to optimize a surgeon's clinic time use and streamline patient care.

Monolignol ferulate conjugates are naturally incorporated into plant lignins.

Angiosperms represent most of the terrestrial plants and are the primary research focus for the conversion of biomass to liquid fuels and coproducts. Lignin limits our access to fibers and represents a large fraction of the chemical energy stored in plant cell walls. Recently, the incorporation of monolignol ferulates into lignin polymers was accomplished via the engineering of an exotic transferase into commercially relevant poplar. We report that various angiosperm species might have convergently evolved to natively produce lignins that incorporate monolignol ferulate conjugates. We show that this activity may be accomplished by a BAHD feruloyl-coenzyme A monolignol transferase, OsFMT1 (AT5), in rice and its orthologs in other monocots.

Adenosine 5'-O-(3-thio)triphosphate (ATPgammaS) is a substrate for the nucleotide hydrolysis and RNA unwinding activities of eukaryotic translation initiation factor eIF4A.

Whereas ATPgammaS is often considered a nonhydrolyzable substrate for ATPases, we present evidence that ATPgammaS is a good substrate for the RNA-stimulated nucleotide hydrolysis and RNA unwinding activities of eIF4A. In the presence of saturating single-stranded poly(U) RNA, eIF4A hydrolyzes ATPgammaS.Mg and ATP.Mg with similar steady-state parameters (KM(NTP.Mg) = 66 and 58 microM and kcat = 1.0 and 0.97 min(-1), respectively). ATPgammaS.Mg also supports catalysis of RNA unwinding within 10-fold of the rate supported by ATP.Mg. The identical steady-state rate parameters, in comparison with the expected difference in the intrinsic rate of hydrolysis for ATP and ATPgammaS, suggest a nonchemical rate-limiting step for nucleotide hydrolysis. These results raise caution concerning the assumption that ATPgammaS is a nonhydrolyzable ATP analog and underscore the utility of thio-substituted NTPs as mechanistic probes.