Genomic expression during human myelopoiesis

<p>Abstract</p> <p>Background</p> <p>Human myelopoiesis is an exciting biological model for cellular differentiation since it represents a plastic process where multipotent stem cells gradually limit their differentiation potential, generating different precursor cells which finally evolve into distinct terminally differentiated cells. This study aimed at investigating the genomic expression during myeloid differentiation through a computational approach that integrates gene expression profiles with functional information and genome organization.</p> <p>Results</p> <p>Gene expression data from 24 experiments for 8 different cell types of the human myelopoietic lineage were used to generate an integrated myelopoiesis dataset of 9,425 genes, each reliably associated to a unique genomic position and chromosomal coordinate. Lists of genes constitutively expressed or silent during myelopoiesis and of genes differentially expressed in commitment phase of myelopoiesis were first identified using a classical data analysis procedure. Then, the genomic distribution of myelopoiesis genes was investigated integrating transcriptional and functional characteristics of genes. This approach allowed identifying specific chromosomal regions significantly highly or weakly expressed, and clusters of differentially expressed genes and of transcripts related to specific functional modules.</p> <p>Conclusion</p> <p>The analysis of genomic expression during human myelopoiesis using an integrative computational approach allowed discovering important relationships between genomic position, biological function and expression patterns and highlighting chromatin domains, including genes with coordinated expression and lineage-specific functions.</p

The use of functional tests and planned coronary angiography after percutaneous coronary revascularization in clinical practice. Results from the AFTER multicenter study

Background: The follow-up strategies after percutaneous coronary intervention (PCI) have relevant clinical and economic implications. The purpose of this prospective observational multicenter study was to evaluate the effect of clinical, procedural and organizational variables on the execution of functional testing (FT) and planned coronary angiography (CA) after PCI, and to assess the impact of American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on clinical practice. Methods: Four hundred twenty consecutive patients undergoing PCI were categorized as class I, IIB and III indications for follow-up FT according to ACC/AHA guidelines recommendations. Furthermore, all patients were grouped according to the presence or absence of FT and/or planned CA over 12 months after PCI. Multivariable analysis was used to assess the potential predictors of test execution. Results: During the 12-month follow-up at least one test was performed in 72% of patients with class I indication, 63% of patients with class IIB indication and 75% of patients with class III indication (p=ns). A total of 283 patients (67%) underwent testing. The use of tests was associated with younger age (R. R. 0.94, C. I. 0.91 +/- 0.97, p<0.001), a lower number of diseased vessels (R.R. 0.60, C.I. 0.43 +/- 0.84, p=0.003), follow-up by the center performing PCI (R. R. 2.64, C. I. 1.43 +/- 4.86, p=0.002), and the specific center at which PCI was performed. Most asymptomatic patients completed their testing prematurely with respect to the risk period for restenosis. Conclusions: The use of FT and planned CA after PCI is unrelated to patient's symptom status, and depends on patient's age and logistics. ACC/AHA guidelines have no influence in clinical practice, and test timing is not tailored to the risk period for restenosis. (C) 2008 Elsevier Ireland Ltd. All rights reserved

A novel mutation in the N-terminal acting-binding domain of Filamin C protein causing a distal myofibrillar myopathy

Variants in Filamin C (FLNC) gene may cause either cardiomyopathies or different myopathies. We describe a family affected by a distal myopathy with autosomal dominant inheritance. The onset of the disease was in the third decade with gait impairment due to distal leg weakness. Subsequently, the disease progressed with an involvement of proximal lower limbs and hand muscles. Muscle biopsy, performed in one subject,identified relevant myofibrillar abnormalities. We performed a target gene panel testing for myofibrillar myopathies by NGS approach which identified a novel mutation in exon 3 of FLNC gene (c.A664G:p.M222V), within the N-terminal actin-binding (ABD) domain. This variant has been identified in all affected members of the family, thus supporting its pathogenic role. Differently from previously identified variants, our family showed a predominant leg involvement and myofibrillar aggregates, thus further expanding the spectrum of Filamin C related myopathies

Incidentally discovered pheochromocytoma and aldosterone-producing adenoma in the same adrenal gland

Simultaneous occurrence of pheochromocytoma and aldosterone-producing adrenocortical tumor has been rarely reported in patients with symptoms or findings suggestive for both neoplasms. Herein, we report and discuss on a challenging case of synchronous pheochromocytoma and aldosterone-producing adenoma incidentally detected in the same adrenal gland and documented by biochemical studies and pathological examination

Psychosocial burden and professional and social support in patients with hereditary transthyretin amyloidosis (ATTRv) and their relatives in Italy

Hereditary transthyretin amyloidosis (hATTR), alias ATTR variant (ATTRv) is a severe and disabling disease causing sensory and motor neuropathy, autonomic dysfunction, and cardiomyopathy. The progressive decline of patient's functional autonomy negatively affects the patient's quality of life and requires increasing involvement of relatives in the patient's daily life. Family caregiving may become particularly demanding when the patient is no longer able to move independently. This study is focused on the psychosocial aspects of ATTRv from the patient and relative perspectives. In particular, it explored: the practical and psychological burdens experienced by symptomatic patients with ATTRv and their key relatives and the professional and social network support they may rely on; whether burden varied in relation to patients' and relatives' socio-demographic variables, patients' clinical variables, and perceived professional and social network support; and, any difference in burden and support between patients and their matched relatives

RFC1 expansions are a common cause of idiopathic sensory neuropathy

After extensive evaluation, one-third of patients affected by polyneuropathy remain undiagnosed and are labelled as having chronic idiopathic axonal polyneuropathy, which refers to a sensory or sensory-motor, axonal, slowly progressive neuropathy of unknown origin. Since a sensory neuropathy/neuronopathy is identified in all patients with genetically confirmed RFC1 cerebellar ataxia, neuropathy, vestibular areflexia syndrome, we speculated that RFC1 expansions could underlie a fraction of idiopathic sensory neuropathies also diagnosed as chronic idiopathic axonal polyneuropathy. We retrospectively identified 225 patients diagnosed with chronic idiopathic axonal polyneuropathy (125 sensory neuropathy, 100 sensory-motor neuropathy) from our general neuropathy clinics in Italy and the UK. All patients underwent full neurological evaluation and a blood sample was collected for RFC1 testing. Biallelic RFC1 expansions were identified in 43 patients (34%) with sensory neuropathy and in none with sensory-motor neuropathy. Forty-two per cent of RFC1-positive patients had isolated sensory neuropathy or sensory neuropathy with chronic cough, while vestibular and/or cerebellar involvement, often subclinical, were identified at examination in 58%. Although the sensory ganglia are the primary pathological target of the disease, the sensory impairment was typically worse distally and symmetric, while gait and limb ataxia were absent in two-thirds of the cases. Sensory amplitudes were either globally absent (26%) or reduced in a length-dependent (30%) or non-length dependent pattern (44%). A quarter of RFC1-positive patients had previously received an alternative diagnosis, including Sj\uf6gren's syndrome, sensory chronic inflammatory demyelinating polyneuropathy and paraneoplastic neuropathy, while three cases had been treated with immune therapies

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81&nbsp;years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Incidenza delle nefropatie e confronto con la loro prevalenza nella popolazione veneta: studio epidemiologico

End Stage Renal Disease (ESRD) is one of the most expensive and frequent disease in Italy. Patients with renal disease are constantly growing all over the world, with some geographic peculiarity. Major causes of CKD are hypertension and diabetes. We have considered all first nephrologic evaluation done in 2010 in a Nephrology and Dialysis Unit of a Veneto Hospital. We take antropometric, anamnestic, clinical, biochemical and imaging record. We used CKD-EPI formula for the evaluation of estimated GFR, in reason to compare the dates with the INCIPE study, an epidemiologic study who determined prevalence of chronic renal disease in Veneto population and used CKD-EPI too. The study demonstrate that CKD incidence is 2360 pmp, about 1/53 of the prevalence; diagnosis is made after a cardiovascular event in about 40% of cases, that it means that serious complications of disease have yet established. We think is of great importance to screen population at risk for nephropathies (people with diabetes, hypertension, obesity, males in particular) and make early referral to nephrologist with eGFR <60 ml/min (CKD III). At this time of natural history of the renal disease is possible to start pharmacological and lifestyle measures to delay progression and complications. Then the nephrologist should have ultrasonografic competence, a skill that will improve diagnosis accuracy.L' insufficienza renale cronica terminale (End Stage Renal Disease, ESRD) rappresenta in Italia una importante voce in termini di spesa socio-sanitaria e di numerosità di pazienti. Gli individui affetti da tale malattia cronica sono in costante aumento anche nel resto del mondo, con modalità peculiari delle diverse aree geografiche. Le principali cause di malattia renale cronica (Chronic Kidney Disease, CKD) sono attualmente l’ ipertensione arteriosa ed il diabete mellito. Durante un intero anno solare sono state reclutate tutte le prime visite nefrologiche effettuate presso l’ambulatorio divisionale di un Reparto di Nefrologia e Dialisi di un ospedale del Veneto. Sono stati raccolti i dati antropometrici, anamnestici, clinici, laboratoristici e strumentali. Per il calcolo del eGFR si è applicata la formula CKD-EPI per qualsiasi valore di creatinina, dal momento che la stessa era stata usata nello studio INCIPE, studio di prevalenza di riferimento condotto sulla popolazione della stessa regione geografica. Lo studio dimostra che l’incidenza della CKD è di 2360 pmp, cioè circa 1/53 della prevalenza; la diagnosi viene posta quando circa il 40% dei pazienti ha già subito un evento cardiovascolare, quindi ha già manifestato serie complicanze della nefropatia. Si rende a nostro avviso auspicabile una sensibilizzazione alla ricerca e diagnosi di CKD nelle popolazioni a rischio (diabetici, ipertesi, obesi, soprattutto maschi) da parte dei clinici, affinché la diagnosi e l’invio al nefrologo avvengano alla CKD III (eGFR<60 ml/min), in modo da porre in atto tutti gli accorgimenti terapeutici al fine di rallentare la progressione dalla malattia e la manifestazione delle complicanze. Infine l’acquisizione da parte dello specialista nefrologo della capacità di utilizzare la metodica ultrasonografica può aumentare l’accuratezza diagnostica

Technology and neuroarchitecture

This paper is part of an ongoing research project involving the Department of Architecture and Design at the University of Genoa, as well as entities from both the professional training and industrial worlds. The primary objective of this research is the development of a tool that is useful both for designers and for users. Based on the concept of smart mock-ups, previously developed by the authors, the focus has been declined on the world of nautical design, with the aim of measuring, through qualitative parameters, the user experience in a built environment, whether it is a relaxing or working environment. The first and fundamental step involves defining the 'state of the user' through a vector of measurable variables using a network of sensors that do not significantly alter the UX with the surrounding space. This article presents the state of the art of techniques and sensors that can be used for research purposes, as well as the proposed experimental setting to verify the initial working hypotheses. Then we will describe how research will move on to obtain an affordable and efficient tool for nautical designers. Here, we will describe different types of methods that can be used in neuroscience, from standard ones (like emotions recognition software based on FACS, or biometric sensors like heart rate variability, galvanic skin response), to modern ones (like the use of electroencephalography, functional magnetic resonance imaging) and eye tracking