Lamin A, which is the main constituent of the nuclear lamina, has a crucial role in maintaining the integrity of the nuclear structure and constitutes a platform for the binding of chromatin and ...transcription factors and is involved in the connection between nucleus and cytoskeleton (i.e. through LINC complex proteins interactions), essential for mechano-signaling 3. The reduction/absence of lamin A led to dysmorphic nuclei in EWS cancer cells, causing a severe mislocalization of the LINC complex, thus disrupting nucleo-cytoskeleton interactions, with a corresponding gain in malignant properties, which resulted in increased invasiveness in EWS in vitro studies. The impact of lamin A was particularly evident against liver metastases that resulted significantly smaller and reduced in the number. ...lamin A upregulation was able to induce a more EWS differentiated phenotype (i.e. expression of neural markers such as NEF-H and b3-tubulin).
Anastomotic leak (AL) is a feared complication of esophago-gastric surgery. Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat postoperative pain. Previous analyses conveyed ...heterogeneous data for colorectal surgery with a tendency toward high risk for AL after NSAIDs administration. In the setting of upper gastrointestinal (GI) surgery data are even more puzzled. The purpose of the present study was to assess whether an association exists between postoperative NSAIDs administration and AL after esophago-gastric surgery. PubMed, MEDLINE, Scopus, and Web of Science were searched up to November 2022. The included studies evaluated outcomes for NSAIDs vs. no NSAIDs administration after esophago-gastric surgery. The primary outcome was anastomotic leak (AL). Risk ratio (RR) and 95% confidence intervals (95% CI) were used to assess pooled effect size and relative inference. Six studies (43,784 patients) were included. The patient age ranged from 31 to 84 years, 82.4% were males and preoperative BMI ranged from 15 to 31 kg/m
2
. Esophagectomy was performed in 95% of patients. NSAIDs were administered in 18,075 (41.3%) patients. The cumulative incidence of AL was similar for NSAIDs vs. no NSAIDs (13.6% vs. 13.4%). The risk for postoperative AL was similar for NSAIDs vs. no NSAIDs administration (RR 1.49; 95% CI 0.81–2.75;
p
= 0.19). The cumulative incidence of postoperative gastrointestinal bleeding (0.36% vs. 0.39%), acute kidney injury (0.62% vs. 0.71%), and in-hospital mortality (2.39% vs. 2.66%) were comparable. NSAIDs administration for postoperative analgesia seems not associated with an increased risk for AL after esophago-gastric surgery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Anorexia nervosa (AN) is a disorder characterized by high levels of cognitive control and behavioral perseveration. The present study aims at exploring inhibitory control abilities and their ...functional connectivity correlates in patients with AN. Inhibitory control – an executive function that allows the realization of adaptive behavior according to environmental contingencies – has been assessed by means of the Stop-Signal paradigm. The study involved 155 patients with lifetime AN and 102 healthy women. A subsample underwent resting-state functional magnetic resonance imaging and was genotyped for COMT and 5-HTTLPR polymorphisms. AN patients showed an impaired response inhibition and a disruption of the functional connectivity of the ventral attention circuit, a neural network implicated in behavioral response when a stimulus occurs unexpected. The 5-HTTLPR genotype appears to significantly interact with the functional connectivity of ventral attention network in explaining task performance in both patients and controls, suggesting a role of the serotoninergic system in mechanisms of response selection. The disruption of the ventral attention network in patients with AN suggests lower efficiency of bottom-up signal filtering, which might be involved in difficulties to adapt behavioral responses to environmental needs. Our findings deserve further research to confirm their scientific and therapeutic implications.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction ...is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.Diet impacts human health, influencing body adiposity and the risk of developing cardiometabolic diseases. The gut microbiome is a key player in the diet-health axis, but while its bacterial fraction is widely studied, the role of micro-eukaryotes, including Blastocystis, is underexplored. We performed a global-scale analysis on 56,989 metagenomes and showed that human Blastocystis exhibits distinct prevalence patterns linked to geography, lifestyle, and dietary habits. Blastocystis presence defined a specific bacterial signature and was positively associated with more favorable cardiometabolic profiles and negatively with obesity (p < 1e-16) and disorders linked to altered gut ecology (p < 1e-8). In a diet intervention study involving 1,124 individuals, improvements in dietary quality were linked to weight loss and increases in Blastocystis prevalence (p = 0.003) and abundance (p < 1e-7). Our findings suggest a potentially beneficial role for Blastocystis, which may help explain personalized host responses to diet and downstream disease etiopathogenesis.
Spontaneous intracerebral hemorrhage (ICH) is a devastating type of stroke with a huge impact on patients and families. Expanded use of oral anticoagulants and ageing population might contribute to ...an epidemiological change. In view of these trends, we planned a study to obtain a contemporary picture and identify early prognostic factors to improve secondary prevention.
This multicenter prospective cohort study included consecutive adult patients with non-traumatic ICH admitted to three academic Italian hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Demographic characteristics, vascular risk profile, clinical data and main radiological characteristics were correlated to 90-day clinical outcome.
Out of 682 patients mean age: 73 ± 14 years; 316 (46.3%) females enrolled in this study, 40% died 86/180 (47.8%) in Salerno, 120/320 (37.5%) in Padova, 67/182 (36.8%) in Reggio Emilia; p < 0.05) and 36% were severely disabled at 90 days. Several factors were associated with a higher risk of poor functional outcome such as antithrombotic drug use, hyperglycemia, previous cerebrovascular accident, low platelet count, and pontine/massive/intraventricular hemorrhage. However, at multivariate analysis only pre-ICH mRS score (OR 30.84), GCS score at presentation (OR 11.88), initial hematoma volume (OR 29.71), and NIHSS score at presentation (OR 25.89) were independent predictors of death and poor functional outcome.
Despite the heterogeneity among centers, this study on ICH has identified four simple prognostic factors that can independently predict patients outcome, stratify their risk, and guide their management.
The aim of this study was to investigate the prognostic role of hematoma characteristics and hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (ICH).
This multicenter ...prospective cohort study enrolled consecutive adult patients with non-traumatic ICH admitted to three Italian academic hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Early noncontrast CT (NCCT) features of the hematoma, including markers of HE, and 3-month outcome were recorded. Multivariable logistic regression analysis was performed to identify predictors of poor outcome.
A total of 682 patients were included in the study mean age: 73 ± 14 years; 316 (46.3%) females. Pontine and massive hemorrhage, intraventricular bleeding, baseline hematoma volume > 15 mL, blend sign, swirl sign, margin irregularity ≥ 4, density heterogeneity ≥ 3, hypodensity ≥ 1, island sign, satellite sign, and black hole sign were associated with a higher risk of mortality and disability. However, at multivariate analysis only initial hematoma volume (OR 29.71) proved to be an independent predictor of poor functional outcome at 3 months.
Simple hematoma volume measured on baseline CT best identifies patients with a worse outcome, while early NCCT markers of HE do not seem to add any clinically significant information.
Background Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in ...modulating the prefrontal cortex, since both DA deficiency and excess negatively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa. Methods All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging. Results We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing. Limitations Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels. Conclusion Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies.
The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic ...role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission. The epigenetic signature, made up of 337 differentially methylated regions, was then integrated with gene and protein expression profiles, leading to a network, where cell-to-cell adhesion and cell-motility pathways were found to be aberrantly activated in relapsed patients. We identified most of these factors as RUNX1-RUNX1T1 targets, with Ras Homolog Family Member (RHOB) overexpression being the core of this network. We documented how RHOB re-organized the actin cytoskeleton through its downstream ROCK-LIMK-COFILIN axis: this increases blast adhesion by stress fiber formation, and reduces mitochondrial apoptotic cell death after chemotherapy treatment. Altogether, our data show an epigenetic heterogeneity within t(8;21)-rearranged AML patients at diagnosis able to influence the program of the chimeric transcript, promoting blast re-emergence and progression to relapse.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Backgroud
Hunter disease is a rare X-linked mucopolysaccharidosis. Despite frequent neurological involvement, characterizing the severe phenotype, neuroimaging studies are scarce.
Objectives
To ...determine frequency and severity of neuroradiological mucopolysaccharidosis-related features; to correlate them with clinical phenotype; to evaluate their natural evolution and the impact of intravenous enzymatic replacement therapy (ERT).
Methods
Sixty nine brain MRI examinations of 36 Italian patients (mean-age 10.4 years; age-range 2.2-30.8; severe phenotype in 22 patients) were evaluated. Twenty patients had multiple MRIs (median follow-up 3.1 years, range 1–16.9): among them 15 had MRIs before and after ERT, six had repeated MRIs without being on ERT and five while on ERT. Perivascular, subarachnoid and ventricle space enlargement, white matter abnormality (WMA) burden, pituitary sella/skull/posterior fossa abnormalities, periodontoid thickening, spinal stenosis, dens hypoplasia, myelopathy, vertebral and intervertebral disc abnormalities were graded by means of dedicated scales.
Results
Perivascular spaces enlargement (89%), WMAs (97%), subarachnoid space enlargement (83%), IIIrd-ventricle dilatation (100%), pituitary sella abnormalities (80%), cranial hyperostosis (19%), craniosynostosis (19%), enlarged cisterna magna (39%), dens hypoplasia (66%), periodontoid thickening (94%), spinal stenosis (46%), platyspondylia (84%) and disc abnormalities (79%) were frequently detected. WMAs, IIIrd-ventricle dilatation and hyperostosis correlated with the severe phenotype (p < 0.05). Subarachnoid spaces and ventricle enlargement, WMAs and spinal stenosis progressed despite ERT, while other MR features showed minimal or no changes.
Conclusions
The spectrum of brain and spine MRI abnormalities in Hunter disease is extremely wide and requires a thorough evaluation. WMAs, atrophy/communicating hydrocephalus and spinal stenosis progress over time and might represent possible disease severity markers for new treatment efficacy assessment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims
Laparoscopic appendectomy (LA) for acute appendicitis (AA) is one of the most performed procedures. The effects of peritoneal lavage (PL) and the reasons to perform it have not been cleared and ...all meta-analyses didn’t show a statistical advantage to prevent infectious complications. This study aims to investigate surgeons’ perceptions during LA, comparing intraoperative findings with histological results, and exploring how surgeons’ subjectivity influences the decision-making process on PL.
Methods
Data were extracted from the two-year data lock from REsiDENT-1 registry, a prospective resident-led multicentre observational trial. This study investigates the relationships between PL and postoperative intraabdominal abscesses (pIAA) introducing a classification for AA to standardize the intraoperative grading. We included pre, intra, and postoperative variables. We applied our classification proposal, used a five-point Likert scale (Ls) to assess subjective LA difficulty and ran a concordance analysis between the assessment of AA and histology. Subsequently, a multivariate logistic regression model was built to find factors influencing PL.
Results
561 patients were enrolled from twenty-one hospitals and 51 residents. 542 procedures were included in the logistic regression analysis and 441 in the concordance analysis, due to missing data. PL was used in 222 LA (39, 6%). We discovered a moderate positive monotonic relationship between surgical evaluation and histology,
p
< 0.001. Despite this, the reliability of the surgeon’s assessment of appendicitis is progressively lower for gangrenous and perforated forms. The increasing grade of contamination, the increasing grade of subjective difficulty and the intraoperative finding of a gangrenous or perforated appendicitis were independent predictors of PL.
Conclusion
This study shows how surgeons’ evaluation of AA severity overestimated more than half of gangrenous or perforated appendices with the perception of a challenging procedure. These perceptions influenced the choice of PL. We proved that the evaluation during LA could be affected by subjectivity with a non-negligible impact on the decision-making process.
Graphical abstract
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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