Endoscopic third ventriculostomy versus ventriculoperitoneal shunt in pediatric and adult population: a systematic review and meta-analysis

Neurosurgical Review - Treatment options for hydrocephalus include endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS). Some ambiguity remains regarding indications, safety,...     

High-order mutants reveal an essential requirement for peroxidases but not laccases in Casparian strip lignification

Lignin has enabled plants to colonize land, grow tall, transport water within their bodies, and protect themselves against various stresses. Consequently, this polyphenolic polymer, impregnating cellulosic plant cell walls, is the second most abundant polymer on Earth. Yet, despite its great physiological, ecological, and economical importance, our knowledge of lignin biosynthesis in vivo, especially the polymerization steps within the cell wall, remains vague—specifically, the respective roles of the two polymerizing enzymes classes, laccases and peroxidases. One reason for this lies in the very high numbers of laccases and peroxidases encoded by 17 and 73 homologous genes, respectively, in Arabidopsis. Here, we have focused on a specific lignin structure, the ring-like Casparian strips (CSs) within the root endodermis. By reducing candidate numbers using cellular resolution expression and localization data and by boosting stacking of mutants using CRISPR-Cas9, we mutated the majority of laccases in Arabidopsis in a nonuple mutant—essentially abolishing laccases with detectable endodermal expression. Yet, we were unable to detect even slight defects in CS formation. By contrast, we were able to induce a complete absence of CS formation in a quintuple peroxidase mutant. Our findings are in stark contrast to the strong requirement of xylem vessels for laccase action and indicate that lignin in different cell types can be polymerized in very distinct ways. We speculate that cells lignify differently depending on whether lignin is localized or ubiquitous and whether cells stay alive during and after lignification, as well as the composition of the cell wall.

Casparian strips (CSs) are highly conserved structures that are a defining feature of the root endodermis in higher plants. That CSs are of a lignin-like nature had been proposed repeatedly since their discovery in the 19th century and was firmly established by modern histological and genetic analyses in the model plant Arabidopsis (1, 2). CSs are strictly localized cell wall impregnations, forming as longitudinal, centrally located belts between endodermal cells. Their highly coordinated and simultaneous appearance in endodermal neighbors leads to the fusion of these belts into a supracellular structure that takes the appearance of a delicate network, due to the very thin primary cell walls of young endodermal cell (100 to 200 nm in width). Using lignin stains, this fine network can be easily overlooked, next to the much more pronounced lignification occurring at the same time in the thick secondary cell walls of protoxylem vessels, only two cell layers below within the vasculature. The CSs therefore represent only a minor fraction of the overall lignin content of a root and are always found in close association to the xylem, making it very difficult to use the classical chemical methods of lignin analysis that are central to the field. Yet, CSs are very attractive for cell biological and genetic analyses for a number of reasons. The endodermis can be observed in very young, 5-d-old seedlings, and it is a relatively peripheral, large cell type that is more easily observed than cell types in the vasculature. Moreover, its highly predictable and restricted lignification allows for meaningful spatial correlations between protein localization and lignin deposition. Finally, the endodermis stays alive during and after the entire process of lignification (3). Using the endodermis as a model, we were able to establish a strong requirement for reactive oxygen species (ROS) production in CS lignification. Knockouts of a single NADPH oxidase, respiratory burst oxidase homolog F (RBOHF), led to a near absence of lignification in the endodermis, as did inhibitor treatments interfering with ROS production or accumulation (2). Intriguingly, RBOHF specifically accumulates at the site of CS formation, which is initiated by the accumulation of CASPARIAN STRIP MEMBRANE DOMAIN PROTEINS (CASPs), small transmembrane scaffold proteins that are thought to recruit RBOHF and other proteins to their site of action. Another class of proteins that appear to be localized by CASPs is type III peroxidases (PER). Among those, PER64 showed an especially strict colocalization with CASP1. Indeed, transfer DNA (T-DNA) insertion- and artificial microRNA (amiRNA)-driven knockout/knockdown of multiple endodermis-expressed and CS-localized peroxidases led to a delay of barrier formation (2), although the severity and nature of lignin defects were not assessed at that time. These findings led to a model whereby CASPs are acting to bring together NADPH oxidase and peroxidase, effectively allowing channel-localized ROS production toward peroxidases, thus ensuring localized and efficient lignification (2). Clearly, localized presence of RBOHF and peroxidases is sufficient for localizing lignification since complementation of monolignol-deficient plants with large amounts of external monolignols did not affect localization of CS formation (1). More recently, we showed that a dedicated receptor pathway in the endodermis can detect defects in the CS diffusion barrier and initiate compensatory, ectopic lignification in cell corners, both by enhancing ROS production from RBOHF and RBOHD and inducing expression of genes, including additional peroxidases and laccases (LAC) (4–6). Our findings demonstrating a strong requirement for ROS production and a partial genetic requirement for peroxidases was in contrast with the finding that LACCASES (LACs) are necessary for lignification of xylem vessels, fibers, and other cell types. LACs are glycosylated, multicopper enzymes that catalyze the oxidation of various phenolic substrates using O₂ as final electron acceptor, not requiring H₂O₂ (7, 8). LAC15 was found to express in seed coats, its loss-of-function mutant displaying a 30% reduction of lignin in seeds (9, 10). LAC4, also called IRREGULAR XYLEM 12 (11), and LAC17 are expressed in vessels and xylary fibers in the stem (12). LAC4 localizes to secondary cell wall domains of proto- and metaxylem vessels, as well as vessels, xylary, and interfascicular fibers of inflorescence stems (12–15). Mutant lines of lac4 and lac4 lac17 have collapsed xylem vessels and reduced lignin content in total stem biomass (12). The reduction in lignin content of the double mutant was further enhanced in the presence of an lac11 mutant, which showed severe developmental defects and stopped growing after developing the two first pair of leaves (16). Finally, LAC15 and LAC7 are expressed in lignifying cells in the context of floral organ abscission, although it was not demonstrated whether mutations of both LACs affected lignin deposition in this context (17). More recently, LAC2 was found to negatively regulate overlignification in the root vasculature upon phosphate and water deficiency. Nevertheless, the exact role of LAC2 in such context was not determined (18).Yet, numerous studies have also provided evidence for participation of PERs in lignification outside of the endodermis. In the Arabidopsis stem xylem vessels, mutations of PERs partially impact lignification (19, 20). It was proposed that both enzymes act sequentially in the lignin polymerization of a same cell type, although it has not been excluded that they individually lignify different cell types (8, 15, 21). Cell cultures of the gymnosperm Norway spruce release lignin polymers into the growth medium (22). Scavenging of H₂O₂ prevents production of this extracellular lignin, and phenolic profiling of the culture media of scavenger-treated cell cultures revealed the accumulation of specific oligolignols (21). This led the authors to propose that H₂O₂-independent enzymes, such as laccases, mediate formation of oligolignols, while peroxidases would be required for further polymerization. However, the authors could not exclude the possibility that in their treatment to scavenge H₂O₂, a residual PERs activity was present (21). Unfortunately, participation of PER in lignification in planta has often been inferred from the use of inhibitors of PERs or H₂O₂ production (2, 23), while genetic evidence could reveal only weak, partial effects on lignification, allowing for the possibility that peroxidases are only peripheral actors of lignification in planta.In addition to PERs, data of cell type-specific gene expression have revealed that LACs are expressed in the endodermis (24–27). Considering the evidence on the role of LACs in lignification, we took advantage of the experimental setup offered by the endodermis to conduct a genetic analysis of LACs in order to determine whether they contribute to lignin polymerization in the CS.In this work, we set out to determine whether one given lignin structure in a cell requires either laccases or peroxidases exclusively or whether its formation requires a combination of both enzyme classes. Using the endodermal CS as a model, we demonstrate that a number of laccases show specific expression in the endodermis and localization to the CS, yet generation of a nonuple mutant, mutating the vast majority of laccases with detectable endodermal expression, had no discernable effect on CS lignification or formation of the endodermal barrier. By contrast, generating a quintuple mutant of endodermis-enriched peroxidases led to a complete absence of CS lignification. Abrogating the compensatory lignification by the SCHENGEN pathway even led to a complete absence of any lignification in young endodermal cells.Based on this, it is most parsimonious to conclude that, despite their strong presence, laccases are fully replaceable for lignification of CS, while peroxidases are absolutely required.     

Predictors of health-related quality of life in neurosurgical brain tumor patients: focus on patient-centered perspective

Background

In brain tumor (BT) patients, the association between health-related quality of life (HRQoL) and psychological characteristics remains largely unknown. We evaluated the association of personality traits, clinical factors, psychological distress symptoms, and cognitive state with HRQoL in BT patients.

Methods

On admission for BT surgery, 200 patients (69 % women; age 55.8?±?14.5 years) were evaluated for HRQoL (SF-36 scale), Big-Five personality traits (Ten-Item Personality Inventory), psychological distress symptoms (Hospital Anxiety and Depression Scale or HADS), cognitive function (Mini-Mental State Examination or MMSE) and clinical characteristics, including functional status (Barthel index or BI). The most common BT diagnoses were meningioma (39 %) and high-grade glioma (18 %).

Results

Only factors significantly associated with SF-36 domains in univariable regression analyses were included in their respective multivariable models and predicted from 6 %–49 % of the total variance of SF-36 scores. Greater TIPI emotional stability score was independently associated with greater SF-36 emotional well-being (β?=?0.23, p?<?0.001) and general health (β?=?0.18, p?=?0.01) scores, and greater TIPI consciousness score, with greater SF-36 emotional well-being score (β?=?0.13, p?=?0.02). HADS-anxiety and HADS-depression scores were the strongest independent determinants of all, except physical functioning, SF-36 scores (β-values range from 0.14 to 0.56; p values?≤?0.03). BI score was the strongest independent determinant of SF-36 physical functioning score (β?=?0.36, p?<?0.001). MMSE score was associated with all but emotional well-being and social functioning SF-36 scores.

Conclusions

Consciousness and emotional stability should be considered important personality-related determinants of HRQoL in BT patients. Psychological distress, functional disability, and cognitive impairment are also important predictors of HRQoL.     

Suicidal ideation in patients undergoing brain tumor surgery: prevalence and risk factors

Purpose

Suicidal ideation (SI) is an important complication in cancer patients that should be promptly recognized and adequately managed. We investigated the prevalence rate and correlates of pre-operative SI in brain tumor (BT) patients admitted for elective BT surgery.

Methods

Two hundred and eleven consecutive patients (70 % women; mean age 55.9 ± 15.4 years) scheduled for BT surgery were evaluated for SI (“suicidal thought” item from the Beck Depression Inventory-II), depressive/anxiety symptom severity (Hospital Anxiety and Depression scale (HADS)), health-related quality of life (SF-36 scale), functional status (Barthel Index), and psychiatric histories and treatments. The majority of patients were diagnosed with meningioma (39 %) and high-grade glioma (17 %).

Results

SI was self-reported by 12 (6 %) patients. Patients expressing SI were most commonly diagnosed with meningioma (50 %). Patients with SI were more likely to have a past history of psychiatric disorders, scored higher on the HADS anxiety subscale, and reported worse health-related quality of life across physical and mental health domains. In multivariate regression analyses, worse perceived mental health was associated with increased risk for SI independently from clinical, sociodemographic, and other patient-oriented variables considered in the study.

Conclusions

SI was self-reported by 6 % of BT patients before surgical intervention and was associated with a past history of psychiatric disorders and worse perceived health status. Poor mental health was an independent correlate of SI. The perception of health status by a patient should be considered as an important determinant of poor mental health in BT patients.

     

Incidence and precipitating factors of delirium after coronary artery bypass grafting

OBJECTIVE: To analyze large contemporary patient population, undergoing on-pump coronary artery bypass grafting at our institution, and identify the prevalence and precipitating factors of delirium development. DESIGN: Baseline demographics, operative data and postoperative outcomes of 1367 consecutive patients were recorded prospectively and analysed using multivariate logistic regression analysis, to determine independent predictors of postoperative delirium development. RESULTS: Delirium was detected in 42 (3.07%) patients. Eight factors: age more than 65 years, peripheral vascular disease, Euroscore>/=5, preoperative IABP support, postoperative blood product usage and postoperative low cardiac output syndrome were independently predicting delirium development after coronary artery bypass procedures. Postoperative delirium was associated with significantly higher mortality rate (16.6% vs. 3.9%, p=0.013), prolonged mechanical ventilation time (9.2+/-3.1 vs. 5.05+/-7.6, p=0.04) and increased length of intensive care unit stay (6.8+/-4.9 vs. 2.0+/-2.7 days, p=0.001). CONCLUSIONS: Delirium is a dangerous complication, prolonging intensive care unit stay and postoperative mortality. Factors associated with delirium development are advanced age, peripheral vascular disease, diminished cardiac function and blood product usage.     

Stereotactic radiosurgery for IDH wild type glioblastoma: an international,multicenter study

Journal of Neuro-Oncology - Isocitrate dehydrogenase (IDH) mutation status is recommended used for diagnosis and prognostication of glioblastoma patients. We studied efficacy and safety of...     

SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area

Background: Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area.

Materials and methods: The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method.

Results: Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380–0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00–39.06) vs. 3.09 (0.02–19.30) and 0.27 (0.00–34.57) vs. 0.75 (0.00–39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49–39.06) mm² vs. 5.02 (0.03–37.06) mm², p = 0.006).

Conclusions: SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease—an area of macular lesion.