Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

Neodymium (Nd) based oxide perovskite nanostructures for photocatalytic and photoelectrochemical water splitting functions.

Neodymium (Nd) based perovskite (Nd1-xCoxFeO3) nanostructures were processed to address the rising energy and environment crisis through offering solutions by photocatalytic and photoelectrochemical (PEC) water splitting reactions. The impact of cobalt (Co) ions on the physicochemical properties of Nd-perovskites were studied using X-ray diffraction (XRD), Raman and electron microscopic instruments. The interaction of metal ions was studied in depth via X-ray photoelectron spectroscopy (XPS). Absorption and photoluminescence signals inferred the optical band gap to be lowered and defect states to increase upon Co substitution. Improved photocatalytic efficacy in Nd1-xCoxFeO3 was evaluated by comparative studies using NdFeO3. Secondly, the enhanced conductivities in Nd1-xCoxFeO3 studied via Nyquist plot was found to be advantageous in photoelectrode fabrication for PEC functions. Time-dependent photocurrent density results affirmed the stability in processed devices. Co ions were also inferred to boost the separation of charge carriers effectively. The improved performance in Nd1-xCoxFeO3 nanostructures were well justified to the successful incorporation of Co ions that sway the Nd-O, Co-O and Co-Fe-O bondings and boost the photon absorption and electronic conductivity to facilitate the observed performance.

Clinical and molecular insights into BCG immunotherapy for melanoma.

The incidence of cutaneous melanoma and the mortality rate of advanced melanoma patients continue to rise globally. Despite the recent success of immunotherapy including ipilimumab and pembrolizumab checkpoint inhibitors, a large proportion of patients are refractory to such treatment modalities. The application of mycobacteria such as Bacillus Calmette-Guérin (BCG) in the treatment of various malignancies, including cutaneous melanoma, has been clearly demonstrated after almost a century of observations and experimentation. Intralesional BCG (IL-BCG) immunotherapy is a highly efficient and cost-effective treatment option for inoperable stage III in-transit melanoma, as recommended in the National Comprehensive Cancer Network Guidelines. IL-BCG has shown great efficacy in the regression of directly injected metastatic melanoma lesions, as well as distal noninjected nodules in immunocompetent patients. Clinical and preclinical studies have shown that BCG serves as a strong immune modulator, inducing the recruitment of various immune cells that contribute to antitumour immunity. However, the specific mechanism of BCG-mediated tumour immunity remains poorly understood. Comparative genome analyses have revealed that different BCG strains exhibit distinct immunological activity and virulence, which might impact the therapeutic response and clinical outcome of patients. In this review, we discuss the immunostimulatory potential of different BCG substrains and highlight clinical studies utilizing BCG immunotherapy for the treatment of cutaneous melanoma. Furthermore, the review focuses on the cellular and molecular mechanisms of the BCG-induced immune responses of both the innate and adaptive arms of the immune system. Furthermore, the review discussed the administration of BCG as a monotherapy or in combination with other immunotherapeutic or chemotherapeutic agents.

Integration of imaging and molecular approaches in selective fetal reduction in twin pregnancies with one carrying a pathogenic genomic aberration.

BACKGROUND/PURPOSE: With the evolution of assisted fertility and prenatal diagnostic technology, the prevalence of multi-fetal pregnancy increased, followed by the demand for prenatal intervention if genomic aberration was detected. How to distinguish the affected foetus from the normal co-twin before selective fetal reduction is therefore challenging. OBJECTIVES: We retrospectively reviewed the cases of dichorionic twins at our centre during 2004-2018, where selective fetal reduction was requested because one foetus carried a pathogenic genomic aberration. Five cases were enrolled, including three foetuses with trisomy 21, one foetus with microduplication and one foetus with microdeletion disorders. METHOD: We labelled the affected foetus by prenatal ultrasound and rapid molecular tools. For the twins without discriminating sonographic features (e.g., the same gender and no distinct placentae), interphase fluorescence in situ hybridization, rapid microarray and short tandem repeat markers were applied to identify the affected foetus. RESULTS: Selective fetal reduction was allocated accurately for all individuals. Two cases delivered at term, while two delivered preterm, and one developed fetal loss of the co-twin. CONCLUSION: We proposed a working scheme of integrating imaging and molecular techniques to correctly identify the affected co-twin before selective fetal reduction to ensure the accuracy of the identification.

Polymer-free biolimus-A9-coated stent for primary percutaneous coronary intervention.

BACKGROUND: The polymer-free biolimus-A9 drug-coated stent (DCS) was reported to have superior safety and efficacy outcomes compared with a bare metal stent in the LEADERS FREE trial of high-bleeding-risk patients with acute coronary syndrome and on dual antiplatelet treatment (DAPT) for 1 month. The aim of this investigation was to evaluate the DCS in a consecutive cohort of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). METHODS: We analyzed data from 164 consecutive STEMI patients who underwent PPCI using the DCS at our institution. The primary efficacy endpoint was clinically indicated target lesion revascularization (ciTLR); the primary safety endpoint was a composite of cardiac death, myocardial infarction, and definite/probable stent thrombosis. Clinical outcomes at 1 year are presented here. RESULTS: The mean age of the patients was 61.5 ± 15.5 years, and 86.6% were male. The median symptom-to-balloon-time was 55 min. In 57.9% of patients (n = 95), the infarct had an anterior location. PPCI achieved Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in 163 of 164 patients (99.4%). All patients were prescribed DAPT for 1 year. At 1 year, ciTLR occurred in 1.2% of patients, the primary safety endpoint was reached in 4.3% of patients, and definite stent thrombosis was noted in 0.6% of patients. CONCLUSION: In this consecutive real-world cohort of patients, the DCS was safe and efficacious when used for PPCI in patients with STEMI.

Comparative genomics of Eucalyptus and Corymbia reveals low rates of genome structural rearrangement.

BACKGROUND: Previous studies suggest genome structure is largely conserved between Eucalyptus species. However, it is unknown if this conservation extends to more divergent eucalypt taxa. We performed comparative genomics between the eucalypt genera Eucalyptus and Corymbia. Our results will facilitate transfer of genomic information between these important taxa and provide further insights into the rate of structural change in tree genomes. RESULTS: We constructed three high density linkage maps for two Corymbia species (Corymbia citriodora subsp. variegata and Corymbia torelliana) which were used to compare genome structure between both species and Eucalyptus grandis. Genome structure was highly conserved between the Corymbia species. However, the comparison of Corymbia and E. grandis suggests large (from 1-13 MB) intra-chromosomal rearrangements have occurred on seven of the 11 chromosomes. Most rearrangements were supported through comparisons of the three independent Corymbia maps to the E. grandis genome sequence, and to other independently constructed Eucalyptus linkage maps. CONCLUSIONS: These are the first large scale chromosomal rearrangements discovered between eucalypts. Nonetheless, in the general context of plants, the genomic structure of the two genera was remarkably conserved; adding to a growing body of evidence that conservation of genome structure is common amongst woody angiosperms.

Association between exposure to household cigarette smoking behavior and cigarette smoking in Hispanic adults: Findings from the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Cigarette smoking behavior is highly determined by social influences during childhood and adolescence. This phenomenon has not been fully evaluated in the Hispanic/Latino population. PURPOSE: To examine the association between exposure to household cigarette smoking behavior (HCSB) and adult cigarette smoking among a diverse Hispanic/Latino population living in four US urban centers. The effect of acculturation on cigarette smoking was also evaluated. METHODS: Data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n=13,231, ages 18-74years, collected between March 2008 and June 2011) were analyzed using logistic regression. RESULTS: HCSB exposure was an independent risk factor for adult current cigarette smoking in Hispanic/Latinos (OR 1.7; 95% CI 1.4, 2.1) after controlling for relevant confounders including socio-demographic and cultural factors. Cubans and Puerto Ricans had the highest prevalence of HCSB exposure (59% and 47% respectively) and highest prevalence of current cigarette smoking (26% and 32%) compared with other Hispanic/Latino groups, (p<.01). CONCLUSIONS: Our data suggest that exposure to HCSB in Hispanics/Latinos living in the US is an independent predictor of adult cigarette smoking, and this association appears to be strongest in Cubans and Puerto Ricans.

Bioactivity of Several Herbicides on the Nanogram Level Under Different Soil Moisture Conditions.

In this study, a double-tube centrifuge method was employed to determine the effects of soil moisture on the bioactivity of cafenstrole, pretilachlor, benfuresate, oxyfluorfen and simetryn. In general, the available herbicide concentration in soil solution (ACSS) showed little change as soil moisture increased for herbicides. The total available herbicide in soil solution (TASS) typically increased as soil moisture increased for all herbicides. The relationship between TASS and % growth rate based on dry weight showed strong linear relationships for both cafenstrole and pretilachlor, with r2 values of 0.95 and 0.84, respectively. Increasing TASS values were consistent with increasing herbicide water solubility, with the exception of the ionizable herbicide simetryn. Plant absorption and % growth rate exhibited a strong linear relationship with TASS. According to the results suggested that TASS was a better predictor of herbicidal bioactivity than ACSS for all herbicides under unsaturated soil moisture conditions.

Bioavailability of the Nano-Unit 14C-Agrochemicals Under Various Water Potential.

The study was conducted to investigate the effects of water potential on bioavailability of the nano-unit 14C-cafenstrole, 14C-pretilachlor, 14C-benfuresate, 14C-simetryn and 14C-oxyfluorfen applied with or without dimepiperate or daimuron under various water potential conditions. The highest bioavailable concentration in soil solution (BCSS) was found at 60% soil moisture, while the lowest occurred at 50% soil moisture for soil-applied alone or in combination. All water potential conditions differed significantly from each other with variations in total bioavailable amount in soil solution (TBSS) when either dimepiperate or daimuron were added to the soil, and changes were directly proportional to variations in water potential. Across all treatments, TBSS at 80% soil moisture was three to four times greater than that at 50% soil moisture when applied alone or in combination with dimepiperate or daimuron. Cafenstrole and simetryn had distribution coefficient (Kd) values <64 ml g-1 and a TBSS ranging from 10 to 44 ng g-1 soil, regardless of water potential conditions applied alone or in combination. Pretilachlor and benfuresate had Kd values <15 ml g-1 and a TBSS range of 38 to 255 ng g-1 soil when applied with or without dimepiperate or daimuron.

Screening Eucalyptus cloeziana and E. argophloia Populations for Resistance to Puccinia psidii.

Disease screening to determine the threat Puccinia psidii poses to plantation and native eucalypts in Australia was undertaken in half-sib families of two contrasting eucalypt species, Eucalyptus cloeziana and E. argophloia. Artificial inoculation with a single-lesion isolate of P. psidii was used to screen these species for resistance to the biotype of P. psidii established in Australia. The objective was to characterize resistance to P. psidii within these two distinct species: E. argophloia, a vulnerable species with a narrow distribution, and E. cloeziana, a species with a broad and extensive distribution in Queensland. Results for E. cloeziana indicate that inland provenances are more resistant to P. psidii infection than provenances from coastal regions. Heritability estimates for the two assessment systems used (resistance on a 1-to-5 ordinal scale verses resistance on a 0-to-1 binomial scale) were low to high (0.24 to 0.63) for E. argophloia and moderate to high (0.4 to 0.91) for E. cloeziana, indicating a significant level of additive genetic variance for rust resistance within the populations. This study demonstrates the potential to select resistant families within the tested populations and indicates that P. psidii could detrimentally affect these species in native forests, nurseries, and plantations.

Spatio-temporal functional data analysis for wireless sensor networks data.

A new methodology is proposed for the analysis, modeling and forecasting of data collected from a wireless sensor network. Our approach is considered in the framework of a functional data analysis paradigm where observed data is represented in a functional form. To reduce dimensionality, functional principal components analysis is applied to highlight important underlying characteristics and find patterns of variations. The principal scores are modeled with tensor product smooths that allow for smoothing over space and time. The model is then used for simultaneous spatial prediction at unsampled locations and to forecast future observations. We consider soil temperature data from a wireless sensor network of 50 sensor nodes in two different land types (grassland and forest) observed during 60 consecutive days in private property close to Yass, New South Wales, Australia.

Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization.

OBJECTIVES: Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases. METHODS: In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1. RESULTS: Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies. CONCLUSION: Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome.

Evaluation of non-additive genetic effects on carcass and meat quality traits in Korean Hanwoo cattle using genomic models.

The traditional genetic evaluation methods generally consider additive genetic effects only and often ignore non-additive (dominance and epistasis) effects that may have contributed to genetic variation of complex traits of livestock species. The available dense single nucleotide polymorphisms (SNPs) panels offer to investigate the potential benefits of including non-additive genetic effects in the genomic evaluation models. Data from 16 971 genotyped (Illumina Bovine 50 K SNP chip) Korean Hanwoo cattle were used to estimate genetic variance components and prediction accuracy of genomic breeding values (GEBVs) for four carcass and meat quality traits: carcass weight (CWT), eye muscle area (EMA), back fat thickness (BFT) and marbling score (MS). Five different genetic models were evaluated through including additive, dominance and epistatic interactions (additive by additive, A × A; additive by dominance, A × D and dominance by dominance, D × D) successively in the models. The estimates of additive genetic variances and narrow sense heritabilities (ha2) were found similar across the evaluated models and traits except when additive interaction (A × A) was included. The dominance variance estimates relative to phenotypic variance ranged from 1.7-3.4% for CWT and MS traits, whereas, they were close to zero for EMA and BFT traits. The magnitude of A × A epistatic heritability (haa2) ranged between 14.8 and 27.7% in all traits. However, heritability estimates for A × D and D × D epistatic interactions (had2 and hdd2) were quite low compared to haa2 and were contributed only 0.0-9.7% of the total phenotypic variation. In general, broad sense heritability (hG2) estimates were almost twice (ranging between 0.54 and 0.68) the ha2 for all of the investigated traits. The inclusion of dominance effects did not improve the prediction accuracy of GEBV but improved 2.0-3.0% when epistatic effects were included in the model. More importantly, rank correlation revealed that partitioning of variance components considering dominance and epistatic effects in the model would enable to re-rank of top animals with better prediction of GEBV. The present result suggests that dominance and epistatic effects could be included in the genomic evaluation model for better estimates of variance components and more accurate prediction of GEBV for carcass and meat quality traits in Korean Hanwoo cattle.

Functional ultrasound imaging of the human spinal cord.

Utilizing the first in-human functional ultrasound imaging (fUSI) of the spinal cord, we demonstrate the integration of spinal functional responses to electrical stimulation. We record and characterize the hemodynamic responses of the spinal cord to a neuromodulatory intervention commonly used for treating pain and increasingly used for the restoration of sensorimotor and autonomic function. We found that the hemodynamic response to stimulation reflects a spatiotemporal modulation of the spinal cord circuitry not previously recognized. Our analytical capability offers a mechanism to assess blood flow changes with a new level of spatial and temporal precision in vivo and demonstrates that fUSI can decode the functional state of spinal networks in a single trial, which is of fundamental importance for developing real-time closed-loop neuromodulation systems. This work is a critical step toward developing a vital technique to study spinal cord function and effects of clinical neuromodulation.

Synthesis and optical characterization of SrHfO3 nano-crystals synthesized by using the combustion method.

We synthesized SrHfO3 nano-crystals (NCs) by using the combustion method, and investigated their emission property using 325 nm photo-excitation. The as-grown SrHfO3 NCs were annealed at different temperatures from 700 degrees C to 1450 degrees C. The X-ray diffraction analysis revealed that all the samples are of a single phase, and the grain size increases with the higher temperature annealing. Interestingly, it is found that in contrast to the bulk case, the SrHfO3 NCs show a strong blue emission even at room temperature. The strong dependence of the visible emission on annealing temperatures and grain sizes indicated that the effects of grain size and oxygen vacancies may play a role in forming the observed visible emission band for SrHfO3 NCs. We also compare our findings with the case of similar material, SrZrO3.

Signatures of DNA flexibility, interactions and sequence-related structural variations in classical X-ray diffraction patterns.

The theory of X-ray diffraction from ideal, rigid helices allowed Watson and Crick to unravel the DNA structure, thereby elucidating functions encoded in it. Yet, as we know now, the DNA double helix is neither ideal nor rigid. Its structure varies with the base pair sequence. Its flexibility leads to thermal fluctuations and allows molecules to adapt their structure to optimize their intermolecular interactions. In addition to the double helix symmetry revealed by Watson and Crick, classical X-ray diffraction patterns of DNA contain information about the flexibility, interactions and sequence-related variations encoded within the helical structure. To extract this information, we have developed a new diffraction theory that accounts for these effects. We show how double helix non-ideality and fluctuations broaden the diffraction peaks. Meridional intensity profiles of the peaks at the first three helical layer lines reveal information about structural adaptation and intermolecular interactions. The meridional width of the fifth layer line peaks is inversely proportional to the helical coherence length that characterizes sequence-related and thermal variations in the double helix structure. Analysis of measured fiber diffraction patterns based on this theory yields important parameters that control DNA structure, packing and function.

Effect of O3 and O3/H2O2 on algae harvesting using chitosan.

We examined the effects of pre-oxidation using ozone (O3) and a combination of O3 and hydrogen peroxide (O3/H2O2) on algae suspensions and their harvesting. Inactivation of algae cells, release of intracellular organic matter (IOM), mineralization of extracellular organic matter (EOM), and changes in molecular weight distribution of EOM were found after pre-oxidation. Enhanced separation efficiency of turbidity, dissolved organic carbon (DOC), protein, and polysaccharide using chitosan and polyaluminum chloride (PACl) was found after pre-oxidation, especially when algae cells were subject to O3/H2O2. Chitosan showed higher efficiency than PACl. Judging from the remarkable increase in floc size, it was proposed that released IOM formed complexes with cationic chitosan and resulted in enhanced dual flocculation and facilitated algae separation.