Influenza vaccine effectiveness for the elderly: a cohort study involving General Practitioners from Abruzzo, Italy

Introduction. In all Italian regions influenza vaccine is routinely administered to the elderly population. However, vaccination impact has been rarely evaluated because of the high costs of conventional cohort investigations. A promising low-cost alter- native approach uses administrative discharge data to derive vaccine effectiveness indicators (hospitalizations and/or deaths) and involves General Practitioners (GPs) to document the exposure. We conducted a cohort analysis using such approach to assess influenza vaccine effectiveness and to investigate the feasibility and validity of that methodology for routine vaccine evaluation. Methods. During October 2006, all GPs from two Local Health Units (LHUs) were requested to indicate immunization status of all their patients in a specific form containing patient?s demo- graphic records. Immunization status information were also collected from Prevention Departments. Main outcomes were hospitalizations for influenza and/or pneumonia. Analyses were based upon random-effect logistic regression. Results. Of a total of 414 GPs assisting 103,162 elderly, 116 GPs (28%) provided data on 32,457 individuals (31.5%). The sample was representative and had an overall 66.2% vaccina- tion rate. During the first semester 2007, the hospitalization rate was low in the sample, with only 7 elderly patients admitted for influenza and 135 for pneumonia. At either bivariate or multi- variate analysis, vaccination did not significantly reduce the risk of in-hospital death, influenza or pneumonia admission. Discussion. The study had minimal costs, recruited a large and representative sample size, and had no evidence of a substantial selection bias. Administrative and GP?s data may be successively pooled to provide routine assessment of vaccination effectiveness

Nuclear phospholipase C β1 signaling, epigenetics and treatments in MDS.

Myelodysplastic syndromes (MDS), clonal hematopoietic stem-cell disorders mainly affecting older adult patients, show ineffective hematopoiesis in one or more of the lineages of the bone marrow. Most MDS are characterized by anemia, and a number of cases progresses to acute myeloid leukemia (AML). Indeed, the molecular mechanisms underlying the MDS evolution to AML are still unclear, even though the nuclear signaling elicited by PI-PLCβ1 has been demonstrated to play an important role in the control of the balance between cell cycle progression and apoptosis in MDS cells. Here we review both the role of epigenetic therapy on PI-PLCβ1 promoter and the changes in PI-PLCβ1 expression in MDS patients treated for anemia.Myelodysplastic syndromes (MDS), clonal hematopoietic stem-cell disorders mainly affecting older adult patients, show ineffective hematopoiesis in one or more of the lineages of the bone marrow. Most MDS are characterized by anemia, and a number of cases progresses to acute myeloid leukemia (AML). Indeed, the molecular mechanisms underlying the MDS evolution to AML are still unclear, even though the nuclear signaling elicited by PI-PLCβ1 has been demonstrated to play an important role in the control of the balance between cell cycle progression and apoptosis in MDS cells. Here we review both the role of epigenetic therapy on PI-PLCβ1 promoter and the changes in PI-PLCβ1 expression in MDS patients treated for anemia. © 2012 Elsevier Ltd

Epigenetic Regulation of Nuclear PI-PLC beta1 Signalling Pathway in Low-Risk MDS Patients During Azacitidine Treatment

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological malignancies characterized by epigenetic abnormalities and therefore treated with demethylating agents [1]. PI-PLCbeta1 has been reported to be a specific target for demethylating therapy in high-risk MDS patients, since azacitidine treatment can be associated with a PI-PLCbeta1 specific promoter demethylation and induction of both PI-PLCbeta1 gene and protein expression [1]. In the present study we investigated the role of epigenetic regulation of PI-PLCbeta1, mainly focusing on the functional role of azacitidine on the structure of the PI-PLCbeta1 promoter. We firstly examined the effect of azacitidine on PI-PLCbeta1 promoter methylation and gene expression in low-risk MDS. Moreover, we studied the expression of key molecules involved in the nuclear inositide signalling pathway, such as Cyclin D3. We also studied the correlation between the demethylating effect of azacitidine and the degree of recruitment to PI-PLCbeta1 promoter of some transcription factors implicated in hematopoietic stem cell proliferation and differentiation, as well as of the Methyl-CpG binding domain proteins (MBDs), which specifically interact with methylated DNA. Taken together, our results hint at a specific involvement of PI-PLCbeta1 in epigenetic mechanisms, and are particularly consistent with the hypothesis of a role for PI-PLCbeta1 in azacitidine- induced myeloid differentiation

Predictors of pain intensity and persistence in a prospective Italian cohort of patients with herpes zoster: relevance of smoking, trauma and antiviral therapy

Herpes zoster (HZ) is a common disease, characterized by rash-associated localized pain. Its main complication, post-herpetic neuralgia (PHN), is difficult to treat and may last for months to years in the wake of rash resolution. Uncertainties remain as to the knowledge of predictors of HZ-related pain, including the role of antiviral therapy in preventing PHN in ordinary clinical practice. This prospective cohort study was aimed at investigating pain intensity at HZ presentation and its correlates, as well as the incidence of PHN and its predictors

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

Role of CREB transcription factor in c-fos activation in natural killer cells

In natural killer (NK) cells, interleukin-2 (IL-2) differentially regulates the expression of several transcription factors, including JunB and c-fos. The cAMP response element binding protein, CREB, is a key transcriptional regulator of a large number of genes containing the octanucleotide CRE consensus sequence in their upstream regulatory regions. We studied here the functional role of CREB in the IL-2-mediated transcriptional regulation of c-fos in human NK cells. Our results show that IL-2 activates CREB in human NK cells and that CREB activation hasa prominent regulatory role on the IL-2-induced expression of functional c-fos and AP-1 in NK cells. We identify two domains of the c-fos promoter, containing three CRE sites, which are critical for the transcriptional activity induced by IL-2. The first domain is located within the first 220 nucleotides of the c-fos promoter, while the second encompasses the nucleotides - 440 and - 220. Our results show that CREB has a relevant role in the cytokine-mediated activation of NK cells, and are particularly remarkable in the light of the several genes that are positively regulated by c-fos and AP-1, such as IFN-gamma, IL-2 and GM-CSF genes

Laminopathies and A-type lamin-associated signalling pathways.

The nuclear envelope (NE) is the most important border in the eukaryotic cells, essential in maintaining the identity of the nuclear and cytoplasmic compartments and in allowing additional levels of regulation and control of the gene expression. Previous studies of our group provided new insights in the complex mechanisms that are involved in the pathogenesis of a group of human diseases, collectively referred to as laminopathies (Maraldi et al., 2003, 2004). In particular, we investigated the influences of disease-causing mutations in A-type lamins on the nuclear morphology and chromatin arrangement (Maraldi et al., 2005, 2006), on the involvement of prelamin A accumulation in progeric laminopathies (Maraldi and Lattanzi, 2007; Maraldi et al., 2007), and on the possible effects of altered lamin A forms on the availability of specific transcription factors (Maraldi et al., 2008). The outer and inner nuclear membranes (ONM and INM, respectively) are characterized by different sets of proteins; in fact, whilst most of the ONM proteins are likely to perform endoplasmic reticulumrelated functions, the roles of INM proteins depend on their interactions with a variety of nuclear proteins, which include lamins, nesprins and chromatin-associated proteins. The INM is associated with two types of lamins, lamin B and lamin A/C, which form the network of filaments of the nuclear lamina. The interactions of many INM proteins with lamins are essential to maintain the stability of the NE. On the other hand, the correct positioning of the nucleus within each cell type is mediated by interaction of nesprins, that span the NE lumen and interact with cytoskeletal elements, and SUNs that interact with the nuclear lamina. Specific interactions of INM proteins and lamins with chromatinassociated proteins are conceivably involved in the organization of the chromatin rrangement. Additional putative functions of the INM proteins and lamins, which are emerging from recent insights, include specific interactions with transcription factors, and modulation of signal transduction pathways. This issue is more than just academic, because defects in lamin and INM protein expression are linked to several human genetic diseases, whose pathogenic mechanisms can be elucidated taking into account the complex functional roles of the NE. Here we discuss the experimental evidence that reveal that the NE functions as a signalling node with an active role in mechanotransduction and suggest a more direct role in gene regulation than previously anticipate

Percutaneous coronary intervention of unprotected left main coronary artery disease as culprit lesion in patients with acute myocardial infarction

ObjectivesThis study sought to evaluate short- and long-term outcomes of patients undergoing emergency percutaneous coronary intervention (PCI) for acute myocardial infarction due to a culprit lesion in an unprotected left main coronary artery.MethodsIn this retrospective, 2-center, international observational study, 5,261 patients were admitted between February 2005 and December 2008 with acute myocardial infarction and treated with PCI; of these, 1,277 were ST-segment elevation myocardial infarction and 3,984 non–ST-segment elevation myocardial infarction. We identified 48 patients among this cohort who underwent emergency PCI to an unprotected left main coronary artery culprit lesion.ResultsMean age was 70 ± 12.5 years, and 45% of the patients presented with ST-segment elevation myocardial infarction or new left bundle branch block. Cardiogenic shock was present in 45%, and distal left main coronary artery disease was present in 71% of patients. Angiographic procedural success was achieved in 92% of patients. Overall in-hospital mortality was 21%, due in all cases to refractory, multiorgan failure. Twenty-five percent experienced major adverse cardiac events, defined as death, myocardial infarction, stent thrombosis, and target vessel revascularization. In patients presenting in cardiogenic shock, in-hospital mortality was 32%. At 1-year follow-up, in-hospital survivors had a mortality rate of 10.5%, whereas 18.4% experienced subsequent major adverse cardiac events. Long-term prognosis was excellent in hospital survivors with a 1-year survival rate of 89.5%.ConclusionsPatients with acute myocardial infarction and thrombosis of the unprotected left main coronary artery are a high-risk subgroup with a substantial mortality, particularly if they present in cardiogenic shock. We demonstrate that in these patients, PCI is a feasible treatment option associated with reasonably good outcomes. Long-term prognosis is excellent in hospital survivors with an 89.5% survival rate at 1 year

Lipid phosphorylation in isolated rat liver nuclei. Synthesis of polyphosphoinositides at subnuclear level.

Isolated rat liver nuclei and subnuclear fractions synthesize polyphosphoinositides in vitro in a mode dependent on the presence of nuclear membrane, detergent and exogenous substrates. The nuclear membrane is not essential as a source of lipid kinases, since the addition of exogenous phosphatidylinositol or phosphatidylinositol monophosphate to reaction mixtures lacking membranes restores the synthesis of phosphatidylinositol mono- and bisphosphate, respectively. Inositide phosphorylation is best accomplished by high-salt extracted nuclei and pre-detergent lamina. These data suggest that the nucleus, and especially the nuclear periphery, is a cell compartment in which polyphosphoinositide synthesis occurs; this might be related to the progression of phosphatidylinositol metabolism-dependent signals to the genetic apparatus