I. II. III. IV. V. VI. References SUMMARY: For survival, plants have to efficiently adjust their phenotype to environmental challenges, finely coordinating their responses to balance growth and ...defence. Such phenotypic plasticity can be modulated by their associated microbiota. The widespread mycorrhizal symbioses modify plant responses to external stimuli, generally improving the resilience of the symbiotic system to environmental stresses. Phytohormones, central regulators of plant development and immunity, are instrumental in orchestrating plant responses to the fluctuating environment, but also in the regulation of mycorrhizal symbioses. Exciting advances in the molecular regulation of phytohormone signalling are providing mechanistic insights into how plants coordinate their responses to environmental cues and mycorrhizal functioning. Here, we summarize how these mechanisms permit the fine‐tuning of the symbiosis according to the ever‐changing environment.
Summary
The International Prognostic Index (IPI) is the most widely used score for non‐Hodgkin lymphoma but lacks the ability to identify a high‐risk population in diffuse large B‐cell lymphoma ...(DLBCL). Low absolute lymphocyte count and high monocytes have proved to be unfavourable factors. Red‐cell distribution width (RDW) has been associated with inflammation and beta‐2 microglobulin (B2M) with tumour load. The retrospective study included 992 patients with DLBCL treated with R‐CHOP. In the multivariate analysis, age, Eastern Cooperative Oncology Group performance status (ECOG‐PS), stage, bulky mass, B2M, RDW, and lymphocyte/monocyte ratio (LMR) were independently related to progression‐free survival (PFS). A new prognosis score was generated with these variables including age categorized into three groups (0, 1, 2 points); ECOG ≥ 3–4 with two; stage III/IV, bulky mass, high B2M, LMR < 2·25 and RDW > 0·96 with one each; for a maximum of 9. This score could improve the discrimination of a very high‐risk subgroup with five‐year PFS and overall survival (OS) of 19% and 24% versus 45% and 59% of R (revised)‐IPI respectively. This score also showed greater predictive ability than IPI. A new score is presented including complete blood cell count variables and B2M, which are readily available in real‐life practice without additional tests. Compared to R‐IPI, it shows a more precise high‐risk assessment and risk discrimination for both PFS and OS.
Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in developed countries. With the aging of population, AMD will become globally an increasingly ...important and prevalent disease worldwide. It is a complex disease whose etiology is associated with both genetic and environmental risk factors. An extensive decline in the quality of life and progressive need of daily living assistance resulting from AMD among those most severely affected highlights the essential role of preventive strategies, particularly advising patients to quit smoking. In addition, maintaining a healthy diet, controlling other risk factors (such as hypertension, obesity, and atherosclerosis), and the use of nutritional supplements (antioxidants) are recommendable. Genetic testing may be especially important in patients with a family history of AMD. Recently, unifying criteria for the clinical classification of AMD, defining no apparent aging changes; normal aging changes; and early, intermediate, and late AMD stages, are of value in predicting AMD risk of progression and in establishing recommendations for the diagnosis, therapeutic approach, and follow-up of patients. The present review is focused on early and intermediate AMD and presents a description of the clinical characteristics and ophthalmological findings for these stages, together with algorithms for the diagnosis and management of patients, which are easily applicable in daily clinical practice.
Importance
To provide a normative vessel density (VD) database for the macula through swept‐source optical coherence tomography angiography (OCTA) and to assess the main determinants of this ...measurement.
Background
In contrast with dye angiography, the recently introduced OCTA technique allows for the non‐invasive measurement of retinal and choroidal VD metrics.
Design
Cross‐sectional study.
Participants
The right eyes of 346 healthy subjects were studied. In 105 subjects both eyes were imaged.
Methods
Foveal and parafoveal macular VD measurements were obtained in the retinal superficial capillary plexus (SCP), deep capillary plexus (DCP), and in the choriocapillaris (CC) layer. Also recorded were age, sex, axial length (AL), foveal and choroidal thickness (CT).
Main Outcome Measures
Normative database and determinants of macular VD measured by OCTA.
Results
Mean participant age was 38.3 ± 20.1 years (mean ± SD) (range 5‐83). Foveal VDs in the different plexuses were: SCP 22.1% ± 5.0% (7.3‐35.1), DCP 19.9% ± 6.3% (6.9‐51.2) and CC: 52.8% ± 4.3% (40.2‐62.1). Parafoveal VDs ranged from 45.4% ± 3.7% to 51.8% ± 4.6%. Positive correlation was observed between foveal VD and foveal thickness (R = .327), as well as between parafoveal DCP VD and CT (R = .250;P ≤ .006), while correlation with age was negative in the SCP and CC (R = −.283;P < .001). No associations were detected between macular VD and sex or AL (P ≥ .05).
Conclusion and Relevance
Macular VD showed wide individual variation, was positively correlated with foveal thickness and with CT, negatively correlated with age, and showed no correlation with AL or sex.
Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder. While most PD cases are idiopathic, the known genetic causes of PD are useful to understand common disease ...mechanisms. Recent data suggests that autophagy is regulated by protein acetylation mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities. The changes in histone acetylation reported to be involved in PD pathogenesis have prompted this investigation of protein acetylation and HAT and HDAC activities in both idiopathic PD and G2019S
leucine-rich repeat kinase 2
(LRRK2) cell cultures. Fibroblasts from PD patients (with or without the G2019S
LRRK2
mutation) and control subjects were used to assess the different phenotypes between idiopathic and genetic PD. G2019S
LRRK2
mutation displays increased mitophagy due to the activation of class III HDACs whereas idiopathic PD exhibits downregulation of clearance of defective mitochondria. This reduction of mitophagy is accompanied by more reactive oxygen species (ROS). In parallel, the acetylation protein levels of idiopathic and genetic individuals are different due to an upregulation in class I and II HDACs. Despite this upregulation, the total HDAC activity is decreased in idiopathic PD and the total HAT activity does not significantly vary. Mitophagy upregulation is beneficial for reducing the ROS-induced harm in genetic PD. The defective mitophagy in idiopathic PD is inherent to the decrease in class III HDACs. Thus, there is an imbalance between total HATs and HDACs activities in idiopathic PD, which increases cell death. The inhibition of HATs in idiopathic PD cells displays a cytoprotective effect.
Ocular neurodegenerative diseases such as glaucoma, diabetic retinopathy, and age-related macular degeneration are common retinal diseases responsible for most of the blindness causes in the ...working-age and elderly populations in developed countries. Many of the current treatments used in these pathologies fail to stop or slow the progression of the disease. Therefore, other types of treatments with neuroprotective characteristics may be necessary to allow a more satisfactory management of the disease. Citicoline and coenzyme Q10 are molecules that have neuroprotective, antioxidant, and anti-inflammatory properties, and their use could have a beneficial effect in ocular neurodegenerative pathologies. This review provides a compilation, mainly from the last 10 years, of the main studies that have been published on the use of these drugs in these neurodegenerative diseases of the retina, analyzing the usefulness of these drugs in these pathologies.
Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, ...despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.
The purpose of this work was to study the relationship between reported traumatic experiences in childhood and positive psychotic symptoms. We hypothesized that dissociative experiences were ...potential mediators between childhood trauma and hallucinations, but not delusions. The sample comprised 71 patients diagnosed with psychoses. They were assessed with the Dissociative Experiences Scale (DES‐II; Carlson & Putnam, 1993), a questionnaire on trauma (TQ; Davidson, Hughes, & Blazer, 1990), and the Positive and Negative Syndrome Scale (PANSS; Kay, Opler, & Lindenmayer, 1988) delusions and hallucinations items. The results showed that childhood trauma was positively associated with the dissociation scale scores (r = .40) and also the hallucination (r = .36) and delusions scale scores (r = .32). Furthermore, it was demonstrated that the dissociation variable was a potential mediator between childhood trauma and hallucinations, but not between childhood trauma and delusions. Of the 3 DES‐II factors, only depersonalization showed a mediating relationship between childhood trauma and hallucinations. The main conclusion is that the impact of childhood trauma on hallucinations may not simply be direct, but mediated by dissociative experiences, especially depersonalization. Clinical implications are also briefly discussed.
The down-regulation of the catalytic subunit of the mitochondrial H+-ATP synthase (beta-F1-ATPase) is a hallmark of most human carcinomas. This characteristic of the cancer cell provides a proteomic ...signature of cellular bioenergetics that can predict the prognosis of colon, lung, and breast cancer patients. Here we show that the in vivo tumor glucose uptake of lung carcinomas, as assessed by positron emission tomography in 110 patients using 2-deoxy-2-18Ffluoro-d-glucose as probe, inversely correlates with the bioenergetic signature determined by immunohistochemical analysis in tumor surgical specimens. Further, we show that inhibition of the activity of oxidative phosphorylation by incubation of cancer cells with oligomycin triggers a rapid increase in their rates of aerobic glycolysis. Moreover, we show that the cellular expression level of the beta-F1-ATPase protein of mitochondrial oxidative phosphorylation inversely correlates (P < 0.001) with the rates of aerobic glycolysis in cancer cells. The results highlight the relevance of the alteration of the bioenergetic function of mitochondria for glucose capture and consumption by aerobic glycolysis in carcinomas.
Up to now, there have been no publication standardizing the digital reconstruction of the modern human ribcage from commingled costo‐vertebral material. Consequently, we designed a validated protocol ...based on anatomical features observed in the literature and the CT scanned ribcages of 10 adult European individuals. After quantifying the shape of these ribcages using 3D geometric morphometrics, we split each vertebra and rib within their corresponding (semi)landmarks. Subsequently, individual bones + (semi)landmarks were imported to LhpFusionBox, commingled and 3D reconstructed. To validate the accuracy of the protocol, we first reconstructed a randomly chosen ribcage three times and then compared these reconstructions to the rest of the sample. Since these reconstructions were closer to their original counterpart than to the others, the remaining sample was reconstructed once. Next, we tested the intra‐observer error during reconstructing using the Procrustes distances among the original ribcages and the reconstructions. We observed that first each ribcage reconstruction was clustered to its original counterpart and second there was a learning curve showing an improvement in the reconstruction process over time. Subsequently, we explored general size and shape differences among the original and reconstructed ribcages through a study of centroid size and a permutation test on the Procrustes distances (10,000 permutations), respectively. Specific shape differences between both groups were further examined through a principal component analysis in shape space. None of these analyses found statistical differences between the original and reconstructed ribcages (p > 0.05). Eventually, we extracted the mean shapes of the original ribcages and the reconstructions in order to visualize potential deviations caused by the anatomical considerations of the researcher. These results demonstrate that the protocol is accurate enough to be used when reconstructing a disarticulated human ribcage.
This manuscript aims to present an accessible protocol for digitally reconstructing the human ribcage from commingled costo‐vertebral remains.
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