Circular RNAs are a large group of RNAs whose cellular functions are still being investigated. We recently proposed that circSMARCA5 acts as sponge for the splicing factor Serine and Arginine Rich ...Splicing Factor 1 (SRSF1) in glioblastoma multiforme (GBM). After demonstrating by RNA immunoprecipitation a physical interaction between SRFS1 and circSMARCA5, we assayed by real-time PCR in a cohort of 31 GBM biopsies and 20 unaffected brain parenchyma controls (UC) the expression of total, pro-angiogenic (Iso8a) and anti-angiogenic (Iso8b) mRNA isoforms of Vascular Endothelial Growth Factor A (VEGFA), a known splicing target of SRSF1. The Iso8a to Iso8b ratio: (i) increased in GBM biopsies with respect to UC (
-value < 0.00001); (ii) negatively correlated with the expression of circSMARCA5 (
-value = -0.46,
-value = 0.006); (iii) decreased in U87-MG overexpressing circSMARCA5 with respect to negative control (
-value = 0.0055). Blood vascular microvessel density, estimated within the same biopsies, negatively correlated with the expression of circSMARCA5 (
-value = -0.59,
-value = 0.00001), while positively correlated with that of SRSF1 (
-value = 0.38,
-value = 0.00663) and the Iso8a to Iso8b ratio (
-value = 0.41,
-value = 0.0259). Kaplan-Meier survival analysis showed that GBM patients with low circSMARCA5 expression had lower overall and progression free survival rates than those with higher circSMARCA5 expression (
-values = 0.033, 0.012, respectively). Our data convincingly suggest that circSMARCA5 is an upstream regulator of pro- to anti-angiogenic VEGFA isoforms ratio within GBM cells and a highly promising GBM prognostic and prospective anti-angiogenic molecule.
Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that ...increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 95% CI, 1.21–1.93) or CVM (hazard ratio, 2.08 95% CI, 1.146–2.97; P<0.001). Cutoff values of SUA able to discriminate total mortality (4.7 mg/dL 95% CI, 4.3–5.1 mg/dL) and CVM status (5.6 mg/dL 95% CI, 4.99–6.21 mg/dL) were identified. The information on SUA levels provided a significant net reclassification improvement of 0.26 and of 0.27 over the Heart Score risk chart for total mortality and CVM, respectively (P<0.001). Sex-specific cutoff values for total mortality and CVM were also identified and validated. In conclusion, SUA levels increasing the risk of total mortality and CVM are significantly lower than those used for the definition of hyperuricemia in clinical practice. Our data provide evidence of a cardiovascular SUA threshold that might contribute in clinical practice to improve identification of patients at higher risk of CVM.
Magnesium and aging Barbagallo, M; Dominguez, L J
Current pharmaceutical design,
03/2010, Letnik:
16, Številka:
7
Journal Article
Recenzirano
Over the past decades, the clinical relevance and biological significance of magnesium (Mg) have been documented. Deficiency in Mg, aside from having a negative impact on the energy production ...pathway required by mitochondria to generate ATP, also reduces the threshold antioxidant capacity of the aging organism and its resistance to free-radical damage. Mg also acts as an antioxidant against free radical damage of the mitochondria. Chronic inflammation and oxidative stress have both been identified as pathogenic factors in aging and in several age-related diseases. Chronic Mg deficiency results in excessive production of oxygen-derived free radicals and low grade inflammation. Aging is very often associated with Mg inadequacy and with increased incidence of many chronic diseases, with muscle loss and sarcopenia, altered immune responses, and vascular and metabolic conditions, such as atherosclerosis, diabetes and the cardiometabolic syndrome. The most common cause of Mg deficit in the elderly population is dietary Mg deficiency, although secondary Mg deficit in aging may also results from many different mechanisms. The aim of the present manuscript is to discuss the mechanisms and consequences of the modifications of Mg metabolism with age, the difficulties in the measurement of Mg status, and to review the current evidences suggesting that age-related chronic Mg deficits may be proposed as one of the physiopathological links that may help to explain the interactions between inflammation, oxidative stress with the aging process and many age-related diseases.
Current evidence shows that cholesterol management either reduces the likelihood of cardiovascular disease (CVD) or slows down its progression. Hence, it is important that all health professionals ...make appropriate use of all the available intervention strategies to control risk factors: from dietary improvement and positive lifestyle changes to the use of functional foods, food supplements, and drugs. This review examines the effect of the most frequently occurring cholesterol-lowering substances in functional foods or in supplements across Europe, namely plant sterols and stanols, monacolin K found in red yeast rice, berberine and beta-glucans. We conclude that currently available supplements and functional foods can effectively reduce plasma LDL cholesterol levels by about 5 to 25%, either alone or in combination. Suitable candidates for these products are mainly individuals at low absolute cardiovascular risk at a young age or according to classic algorithms. Of note, despite being freely available for purchase, these products should be used following shared agreement between the physician and the patient (“concordance”).
Purpose
To analyze the prospectively collected data in a series of patients treated with single- or multilevel ACDF with a stand-alone, zero-profile device, focusing on clinico-radiological outcome, ...complications and technical hints, and to review the literature on such new devices.
Methods
Eighty-five patients harboring symptomatic DDD underwent ACDF with the Zero-P cage-plate: 29 at 1-level and 56 at 2–4 levels (total 162 devices). In the multilevel group, 9 patients received a combination of Zero-P and stand-alone cages (hybrid implants). This study focuses on 32 patients with follow-up ranging from 20 to 48 months. NDI, SF-36 and arm pain VAS scores were registered preoperatively and at follow-up visits. Dysphagia was assessed using the Bazaz score. Imaging included X-rays, CT and MRI, also to assess the presence of vertebral body fractures in multilevel cases. Paired Student
t
test was used for statistical analysis.
Results
SF-36 and NDI showed a statistically significant improvement (
p
< 0.01) and mean arm pain VAS score decreased from 79 to 41. X-rays and CT demonstrated, respectively, a 94.5 % and a 92 % fusion rate. Three patients complained of moderate and two of mild transient dysphagia (15.5 %). No device-related complications occurred and no fractures, secondary to four screws insertion in one vertebral body (i.e., swiss cheese effect), were detected in multilevel cases. In patients with extensive anterior osteophytes only a “focal spondylectomy” was required.
Conclusion
The Zero-P device is safe and efficient, even in multilevel cases. Dysphagia is minimal, extensive anterior osteophytectomy is unnecessary and technical hints may ease the surgical workflow. This is the largest series, with the longest follow-up, reported.
Purpose
Retro-odontoid pseudotumor, not related to inflammatory or traumatic conditions, is an uncommon pathology. Atlanto-axial instability has been advocated to explain the pathophysiology of ...retro-odontoid pseudotumor’s formation and growth. Despite pseudotumor direct removal through transoral or lateral approach represented the main surgical strategy for a long time, in the last decade several authors highlighted the possibility to treat retro-odontoid pseudotumor by occipito-cervical or C1–C2 fixation without removal of the intracanalar tissue. The goal of this study is to analyze the data collected in a series of patients suffering from cervical myelopathy due to non-inflammatory, degenerative retro-odontoid pannus and treated by posterior C1–C2 fixation. The relevant literature is also reviewed.
Methods
Five patients, not suffering from inflammatory diseases, were treated between 2009 and 2012. Abnormalities of cranio-cervical junction and/or lower cervical spondylotic degeneration were observed in all patients. No evidence of atlanto-axial instability was demonstrated. Clinical and radiological evaluation included pre- and post-operative Nurick score as well as pre- and post-operative X-rays, CT and MRI. In one case, CT scan highlighted an eggshell calcification of the pannus. All patients underwent either a C1–C2 fixation (C1 lateral mass and C2 isthmus-pedicle screws) or occipito-cervical fixation (2 patients) in cases of C0–C1 fusion.
Results
Follow-up ranges from 22 to 45 months (mean 32) in four patients. One patient died of surgery-unrelated disease. Nurick score changes suggest a clinical improvement in four cases. Neuro-radiological evaluation shows a progressive but incomplete reduction of thickness of retro-odontoid pseudotumor in one patient, and its disappearance in the other three cases. A second-stage transoral or posterior lateral approach was not required.
Conclusion
Although the etiopathogenesis of non-inflammatory, i.e., degenerative, retro-odontoid pseudotumor is still controversial, our series (the second largest on degenerative retro-odontoid pannus in the literature) confirms that a posterior approach may be sufficient and transoral surgery is not required.
OBJECTIVE:The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad-hoc study aimed at searching for prognostic cut-off values of ...serum uric acid (SUA) in predicting fatal myocardial infaction (MI) in women and men.
METHODS:The URic acid Right for heArt Health study is a nationwide, multicentre, observational cohort study involving data on individuals aged 18–95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 122.3 ± 66.9 months.
RESULTS:A total of 23 467 individuals were included in the analysis. Cut-off values of SUA able to discriminate MI status were identified by mean of receiver operating characteristic curves in the whole database (>5.70 mg/dl), in women (>5.26 mg/dl) and in men (>5.49 mg/dl). Multivariate Cox regression analyses adjusted for confounders (age, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol and use of diuretics) identified an independent association between SUA and fatal MI in the whole database (hazard ratio 1.381, 95% confidence intervals, 1.096–1.758, P = 0.006) and in women (hazard ratio 1.514, confidence intervals 1.105–2.075, P < 0.01), but not in men.
CONCLUSION:The results of the current study confirm that SUA is an independent risk factor for fatal MI after adjusting for potential confounding variables, and demonstrate that a prognostic cut-off value associated to fatal MI can be identified at least in women.
Anterior cervical discectomy and fusion (ACDF) still represents the first surgical option in the treatment of cervical degenerative disc disease (DDD) but is still burdened by several complications ...secondary to the loss of mobility at the treated segment and adjacent segment diseases (ASDs). To overcome those complications, hybrid surgery (HS) incorporating ACDF and cervical disc arthroplasty (CDA) is increasingly performed for DDD.
We retrospectively reviewed the clinical, surgical, and outcome data of 85 consecutive patients (M/F, 41/44) harboring cervical disc herniation with or without osteophytes, with radiculopathy and with or without myelopathy, who underwent the anterior approach to a cervical discectomy on two or more levels with at least one disc prosthesis, along with a cage and plate or an O Profile screwed plate.
All the patients improved regardless of the cervical construct used. No significant relationship between different kinds of prosthesis and their surgical level; the number of cages; and the site of the cages (screwed and/or plated) was found concerning immediate stability, dynamic prosthesis effectiveness, and clinical improvement in all the patients up to the maximum follow-up time.
Although the optimal surgical technique for cervical DDD remains controversial, HS represents a safe and effective procedure in select patients with multilevel cervical DDD, as demonstrated by biomechanical and clinical studies and the present series.
OBJECTIVE:To assess the prognostic cut-off values of serum uric acid (SUA) in predicting fatal and morbid heart failure in a large Italian cohort in the frame of the Working Group on Uric Acid and ...Cardiovascular Risk of the Italian Society of Hypertension.
METHODS:The URic acid Right for heArt Health (URRAH) study is a nationwide, multicentre, cohort study involving data on individuals aged 18–95 years, recruited on a community basis from all regions of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 128 ± 65 months. Incident heart failure was defined on the basis of International Classification of Diseases Tenth Revision codes and double-checked with general practitioners and hospital files. Multivariate Cox regression models having fatal and morbid heart failure as dependent variables, adjusted for sex, age, SBP, diabetes, estimated glomerular filtration rate, smoking habit, ethanol intake, BMI, haematocrit, LDL cholesterol, previous diagnosis of heart failure and use of diuretics as possible confounders, were used to search for an association between SUA as a continuous variable and heart failure. By means of receiver operating characteristic curves, two prognostic cut-off values (one for all heart failure and one for fatal heart failure) were identified as able to discriminate between individuals doomed to develop the event. These cut-off values were used as independent predictors to divide individuals according to prognostic cut-off values in a multivariate Cox models, adjusted for confounders.
RESULTS:A total of 21 386 individuals were included in the analysis. In Cox analyses, SUA as a continuous variable was a significant predictor of all hazard ratio 1.29 (1.23–1.359), P < 0.0001 and fatal hazard ratio 1.268 (1.121–1.35), P < 0.0001 incident heart failure. Cut-off values of SUA able to discriminate all and fatal heart failure status were identified by mean of receiver operating characteristic curves in the whole databaseSUA more than 5.34 mg/dl (confidence interval 4.37–5.6, sensitivity 52.32, specificity 63.96, P < 0.0001) was the univariate prognostic cut-off value for all heart failure, whereas SUA more than 4.89 mg/dl (confidence interval 4.78–5.78, sensitivity 68.29, specificity 49.11, P < 0.0001) for fatal heart failure. The cut-off for all heart failure and the cut-off value for fatal heart failure were accepted as independent predictors in the Cox analysis models, the hazard ratios being 1.645 (1.284–2.109, P < 0.0001) for all heart failure and 1.645 (1.284–2.109, P < 0.0001) for fatal heart failure, respectively.
CONCLUSION:The results of the current study confirm that SUA is an independent risk factor for all heart failure and fatal heart failure, after adjusting for potential confounding variables and demonstrate that a prognostic cut-off value can be identified for all heart failure (>5.34 mg/dl) and for fatal heart failure (>4.89 mg/dl).
Public health messaging during disasters help to provide knowledge and guidance for preventative behaviours and risk reduction. The aim of this review is to explore how public health messages are ...currently being provided during disasters and identify what influencing factors contribute to the effectiveness of these messages.
Scoping review.
A scoping review was conducted using guidance from Joanna Briggs Methodology for Scoping Reviews. A narrative synthesis was utilised due to the heterogeneity of findings. The review included seventeen sources, addressing a variety of disasters around the globe over the past two decades.
Three key influencing factors were identified and are illustrated in a concept model called the Audience, Information, Messenger and Mode (AIMM) Public Health Messaging Scale. This conceptual model depicts considerations such as the quantity, quality, and framing of information, the human and technological sources used for delivery and the audience needs and capabilities required for optimal message impact and effectiveness.
Public health messages do influence prevention behaviours during disasters, but they must be carefully tailored and delivered to ensure adequate reach, comprehension, and compliance.
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