HPV Vaccination in Young Males: A Glimpse of Coverage, Parental Attitude and Need of Additional Information from Lombardy Region, Italy.

Background: In the Lombardy Region, Italy, HPV vaccination is recommended and offered free of charge to 12-years-old males since 2017. The expected vaccination thresholds are still far to be reached. Methods: A cross-sectional survey to investigate parents' attitudes towards the HPV vaccine and knowledge about HPV was administered to parents of boys aged 6 to 18 years attending a large pediatric hospital for outpatient specialistic evaluations. Two parallel multiple logistic regression analyses were conducted to estimate the odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) for attitude towards HPV vaccination and perceived need for more information about HPV vaccination. Results: A positive attitude towards HPV vaccination was found in 74% of interviewed parents. Knowledge of HPV, having a generally positive attitude toward vaccination, and mothers filling in the survey were positively associated with a positive attitude to the HPV vaccine. Parents' perceived need for more information about HPV vaccination was positively associated with the child's age, general positive attitude toward vaccination, Christian religion, and positive attitude toward HPV vaccination; knowing that HPV vaccination is free of charge significantly reduced the risk of asking for more information on HPV vaccination. Conclusions: The majority of parents of male children and adolescents in our study have a positive attitude toward HPV vaccination. Attitude toward HPV vaccination and perceived need for more information on HPV vaccination were directly related to a positive attitude toward vaccines in general. In addition, knowledge of HPV and related pathologies favors a positive attitude toward HPV vaccination. Future health programs should target an even wider diffusion of evidence-based information on vaccines in general and on the HPV vaccine in young males, to support a positive attitude toward vaccines in the general population.

Acute Inflammation and Elevated Cardiac Markers in a Two-Month-Old Infant with Severe Acute Respiratory Syndrome Coronavirus 2 Infection Presenting with Cardiac Symptoms.

Severe acute respiratory syndrome coronavirus 2 infection in children mainly shows a milder course. In complicated cases, it is unknown whether inflammation is predictive of disease severity, as in adults. Moreover, cardiac involvement is anecdotally described. We report the case of a 2-month-old infant with severe acute respiratory syndrome coronavirus 2 infection presenting with fever, tachycardia and elevated interleukin-6, who was diagnosed with myocarditis and treated with immunoglobulins.

Qualitative interviews with healthcare staff in four European countries to inform adaptation of an intervention to increase chlamydia testing.

OBJECTIVE: To determine the needs of primary healthcare general practice (GP) staff, stakeholders and trainers to inform the adaptation of a locally successful complex intervention (Chlamydia Intervention Randomised Trial (CIRT)) aimed at increasing chlamydia testing within primary healthcare within South West England to three EU countries (Estonia, France and Sweden) and throughout England. DESIGN: Qualitative interviews. SETTING: European primary healthcare in England, France, Sweden and Estonia with a range of chlamydia screening provision in 2013. PARTICIPANTS: 45 GP staff, 13 trainers and 18 stakeholders. INTERVIEWS: The iterative interview schedule explored participants' personal attitudes, subjective norms and perceived behavioural controls around provision of chlamydia testing, sexual health services and training in general practice. Researchers used a common thematic analysis. RESULTS: Findings were similar across all countries. Most participants agreed that chlamydia testing and sexual health services should be offered in general practice. There was no culture of GP staff routinely offering opportunistic chlamydia testing or sexual health advice, and due to other priorities, participants reported this would be challenging. All participants indicated that the CIRT workshop covering chlamydia testing and sexual health would be useful if practice based, included all practice staff and action planning, and was adequately resourced. Participants suggested minor adaptations to CIRT to suit their country's health services. CONCLUSIONS: A common complex intervention can be adapted for use across Europe, despite varied sexual health provision. The intervention (ChlamydiA Testing Training in Europe (CATTE)) should comprise: a staff workshop covering sexual health and chlamydia testing rates and procedures, action planning and patient materials and staff reminders via computer prompts, emails or newsletters, with testing feedback through practice champions. CATTE materials are available at: www.STItraining.eu.

Hsp10 nuclear localization and changes in lung cells response to cigarette smoke suggest novel roles for this chaperonin.

Heat-shock protein (Hsp)10 is the co-chaperone for Hsp60 inside mitochondria, but it also resides outside the organelle. Variations in its levels and intracellular distribution have been documented in pathological conditions, e.g. cancer and chronic obstructive pulmonary disease (COPD). Here, we show that Hsp10 in COPD undergoes changes at the molecular and subcellular levels in bronchial cells from human specimens and derived cell lines, intact or subjected to stress induced by cigarette smoke extract (CSE). Noteworthy findings are: (i) Hsp10 occurred in nuclei of epithelial and lamina propria cells of bronchial mucosa from non-smokers and smokers; (ii) human bronchial epithelial (16HBE) and lung fibroblast (HFL-1) cells, in vitro, showed Hsp10 in the nucleus, before and after CSE exposure; (iii) CSE stimulation did not increase the levels of Hsp10 but did elicit qualitative changes as indicated by molecular weight and isoelectric point shifts; and (iv) Hsp10 nuclear levels increased after CSE stimulation in HFL-1, indicating cytosol to nucleus migration, and although Hsp10 did not bind DNA, it bound a DNA-associated protein.

Immunolocalization of poly ADP-ribose on Drosophila polytene chromosomes.

Poly ADP-ribosylation (PARylation) is a posttranslational protein modification catalyzed by poly -ADP-ribose polymerases (PARPs). Poly ADP-ribose metabolism is involved in a wide range of biological processes, such as maintenance of genome stability, transcriptional regulation, energy metabolism, and programed cell death. Recently, chromatin components, including histones, have been shown to be targets of PARylation. Unlike mammals, which have several PARP-encoded genes, the model organism Drosophila melanogaster has only one PARP gene, highly related to mammalian PARP1. These features make flies a great model system to study PARP biology. Commercially available antibodies recognizing this covalent modification have made possible the development of immunofluorescence approaches to study PARylation of chromatin components. Here, we present a protocol to immunostain polytene chromosomes of the model system D. melanogaster.

Genome-wide characterization of chromatin binding and nucleosome spacing activity of the nucleosome remodelling ATPase ISWI.

The evolutionarily conserved ATP-dependent nucleosome remodelling factor ISWI can space nucleosomes affecting a variety of nuclear processes. In Drosophila, loss of ISWI leads to global transcriptional defects and to dramatic alterations in higher-order chromatin structure, especially on the male X chromosome. In order to understand if chromatin condensation and gene expression defects, observed in ISWI mutants, are directly correlated with ISWI nucleosome spacing activity, we conducted a genome-wide survey of ISWI binding and nucleosome positioning in wild-type and ISWI mutant chromatin. Our analysis revealed that ISWI binds both genic and intergenic regions. Remarkably, we found that ISWI binds genes near their promoters causing specific alterations in nucleosome positioning at the level of the Transcription Start Site, providing an important insights in understanding ISWI role in higher eukaryote transcriptional regulation. Interestingly, differences in nucleosome spacing, between wild-type and ISWI mutant chromatin, tend to accumulate on the X chromosome for all ISWI-bound genes analysed. Our study shows how in higher eukaryotes the activity of the evolutionarily conserved nucleosome remodelling factor ISWI regulates gene expression and chromosome organization genome-wide.

The nucleosome-remodeling ATPase ISWI is regulated by poly-ADP-ribosylation.

ATP-dependent nucleosome-remodeling enzymes and covalent modifiers of chromatin set the functional state of chromatin. However, how these enzymatic activities are coordinated in the nucleus is largely unknown. We found that the evolutionary conserved nucleosome-remodeling ATPase ISWI and the poly-ADP-ribose polymerase PARP genetically interact. We present evidence showing that ISWI is target of poly-ADP-ribosylation. Poly-ADP-ribosylation counteracts ISWI function in vitro and in vivo. Our work suggests that ISWI is a physiological target of PARP and that poly-ADP-ribosylation can be a new, important post-translational modification regulating the activity of ATP-dependent nucleosome remodelers.

Genetic identification of a network of factors that functionally interact with the nucleosome remodeling ATPase ISWI.

Nucleosome remodeling and covalent modifications of histones play fundamental roles in chromatin structure and function. However, much remains to be learned about how the action of ATP-dependent chromatin remodeling factors and histone-modifying enzymes is coordinated to modulate chromatin organization and transcription. The evolutionarily conserved ATP-dependent chromatin-remodeling factor ISWI plays essential roles in chromosome organization, DNA replication, and transcription regulation. To gain insight into regulation and mechanism of action of ISWI, we conducted an unbiased genetic screen to identify factors with which it interacts in vivo. We found that ISWI interacts with a network of factors that escaped detection in previous biochemical analyses, including the Sin3A gene. The Sin3A protein and the histone deacetylase Rpd3 are part of a conserved histone deacetylase complex involved in transcriptional repression. ISWI and the Sin3A/Rpd3 complex co-localize at specific chromosome domains. Loss of ISWI activity causes a reduction in the binding of the Sin3A/Rpd3 complex to chromatin. Biochemical analysis showed that the ISWI physically interacts with the histone deacetylase activity of the Sin3A/Rpd3 complex. Consistent with these findings, the acetylation of histone H4 is altered when ISWI activity is perturbed in vivo. These findings suggest that ISWI associates with the Sin3A/Rpd3 complex to support its function in vivo.

Cloning of a rat-specific long PCP4/PEP19 isoform.

We report the identification of a cDNA that encodes a putative protein of 94 amino acids and expected molecular weight of 10.7 kDa, the C-terminal half of which is identical to that of PEP19, a small, brain-specific protein involved in Ca++/calmodulin signaling. The novel rat-specific protein, tentatively named long PEP19 isoform (LPI), is the product of alternative splicing of the rat PCP4 gene encoding PEP19. We found that antibodies raised against the first 13 N-terminal amino acids of LPI, not present in PEP19, recognize a protein enriched in the developing rat brain.

A prospective study of cardiovascular disease in patients with Type 2 diabetes. 6.3 years of follow-up.

OBJECTIVE: Type 2 diabetes mellitus (DM-2) is an important cardiovascular risk factor, although hardly any data are available in our country. Therefore, we decided to study the incidence of cardiovascular disease (CVD) and the related variables with its appearance in a group of patients with DM-2. RESEARCH DESIGN AND METHODS: 176 DM-2 patients without CVD at baseline (63.6% women, mean age 54+/-8.9), mean follow-up 6.3 years. We collected data at 6-month intervals concerning new micro- and macrovascular complications, glucose, HbA(1C), lipid profile, and renal function. We analyzed values at baseline and at the end of follow-up. For numeric variables, the mean value during follow-up was calculated. In renal function variables, we also worked out the difference between baseline and final values, considering the time until the first episode of CVD as the independent variable. Kaplan-Meier analysis was used in categorical variables and Cox regression tests for numeric data and also for multivariate analysis. In multivariate analysis, we included significant data in the univariate analysis, excluding those from the end of the follow-up with the aim of having some predictive meaning in our results. RESULTS: New episodes of CVD were detected in 28 patients (15.9%). These events were statistically related with baseline diagnosed hypertension, presence of diabetic nephropathy and retinopathy, HbA(1C), and total cholesterol. Among mean values during follow-up, the association was with HbA(1C), cholesterol, urinary albumin excretion rate (UAER), glomerular filtration rate (GFR), and systolic arterial pressure. There was also a relationship of CVD events with the new appearance or worsening of diabetic retinopathy or nephropathy, creatinine and UAER increase and the decrease of GFR and effective renal plasma flow (ERPF), during follow-up. In the multivariate analysis, we found an independent association with the appearance of CVD and mean HbA(1C), mean UAER and the presence of proliferative diabetic retinopathy at baseline. CONCLUSIONS: We have a rather low incidence of CVD in our patients with DM-2. The appearance of CVD is independently related with HbA(1C), the level of UAER, and the presence at baseline of diabetic retinopathy.