Densità di popolazione e SARS-CoV-2: uno studio epidemiologico di urban health.

Despite SARS-CoV-2 transmission being a complex phenomenon, greater population density seems to be a risk factor. The aim of this study was to analyze through an epidemiologic urban health approach the relationship between population density and SARS-CoV-2 incidence using data which are comparable with regard to testing strategies. All 10,300 SARS-CoV-2 confirmed cases between October and December 2020 were included. We conducted separate analysis by gender standardizing and stratifying by age and month. In the Province Capital (p.d.=765 inhabitants/km2), standardized SARS-CoV-2 incidence rate was higher than the expected, both in men (SIR=1.17, 95%CI=1.12;1.22, p<0.0001) and women (SIR=1.20, 95%CI=1.15;1.25, p<0.0001). In municipalities with p.d. >200 inhabitants/km2, standardized SARS-CoV-2 incidence rate was similar to the expected (p>0.05). In municipalities with p.d. <200 inhabitants/km2, standardized SARS-CoV-2 incidence rate was lower than the expected, both in men (SIR=0.85, 95%CI=0.81;0.90, p<0.0001) and women (SIR=0.84, 95%CI=0.80;0.88, p<0.0001). Stratified analysis by months with likelihood ratio test showed heterogeneity of the p.d. effect in men and women (p<0.05). SARS-CoV-2 incidence rate seemed to be higher in most densely populated areas, both in men and women. Our results confirmed the great importance of restrictive measures as well as the importance of limiting the epidemic wave in the initial stages and could help guide pandemic management strategies according to urban context and population density.

Lattice Corneal Dystrophy-Variant: a report of three new cases due to p.V631D mutation in the TGFBI gene.

PURPOSE: To report clinical findings and molecular defect in three subjects affected by Biber-Haab-Dimmer dystrophy or Lattice Corneal Dystrophy Type I (LCD1), a corneal dystrophy transmitted as an autosomal dominant tract. MATERIALS AND METHODS: Three subjects underwent a complete ophthalmic examination and confocal microscopy study. Following the collection of DNA from the patients, the TGFBI gene was screened for mutations by direct sequencing. RESULTS: Confocal microscopy study revealed that the opacity typical of the disease was assembled in the axial region of the cornea. The causative TGFBI mutation p.Val631Asp was identified in all subjects. CONCLUSIONS: The finding of the p.Val631Asp mutation responsible for this form of LCD-Variant highlights the utility of molecular genetic analysis of the TGFBI gene in order to offer early diagnosis. These results provide more data for molecular diagnosis and prognosis of this clinical and genetic heterogeneous disease.

Clinical, biochemical and molecular characterization of cystinuria in a cohort of 12 patients.

Cystinuria is a rare autosomal inherited disorder characterized by impaired transport of cystine and dibasic aminoacids in the proximal renal tubule. Classically, cystinuria is classified as type I (silent heterozygotes) and non-type I (heterozygotes with urinary hyperexcretion of cystine). Molecularly, cystinuria is classified as type A (mutations on SLC3A1 gene) and type B (mutations on SLC7A9 gene). The goal of this study is to provide a comprehensive clinical, biochemical and molecular characterization of a cohort of 12 Portuguese patients affected with cystinuria in order to provide insight into genotype-phenotype correlations. We describe seven type I and five non-type I patients. Regarding the molecular classification, seven patients were type A and five were type B. In SLC3A1 gene, two large genomic rearrangements and 13 sequence variants, including four new variants c.611-2A>C; c.1136+44G>A; c.1597T (p.Y533N); c.*70A>G, were found. One large genomic rearrangement was found in SLC7A9 gene as well as 24 sequence variants including 3 novel variants: c.216C>T (p.C72C), c.1119G>A (p.S373S) and c.*82C>T. In our cohort the most frequent pathogenic mutations were: large rearrangements (33.3% of mutant alleles) and a missense mutation c.1400T>C (p.M467T) (11.1%). This report expands the spectrum of SLC3A1 and SLC7A9 mutations and provides guidance in the clinical implementation of molecular assays in routine genetic counseling of Portuguese patients affected with cystinuria.

[Environmental and biological monitoring of exposure to PAHs in Taranto coke-oven workers and in two groups of the general population from Apulia]. / Monitoraggio ambientale e biologico dell'esposizione a IPA nei lavoratori della cokeria di Taranto e confronto con due gruppi della popolazione generale pugliese.

The exposure to PAHs was assessed by personal air sampling and urinary 1-hydroxypyrene (1-OHP) in 100 coke-oven workers (CW) of the Taranto plant and in subjects from the general population living close (NC, 18) and far away (FC, 15) from the plant. Median airborne benzo[a]pyrene (BaP) and 1-OHP levels were 152, 1.5, and 3.6 ng/m3 and 2.0, 0.5 and 0.6 microg/g creatinine in CW, NC, and FC, respectively. BaP exposure exceeded the German acceptable (70 ng/m3) and tolerable (700 ng/m3) limit risk based values in 82 and 11% of CW and the European target value for ambient air (1 ng/m3) in about 65% of NC and FC. 1-OHP levels exceed the proposed biological limit value for the coke-oven industry (4.4 microg/g crt) in 21% of CW and the Italian reference value (0.3 microg/g crt) in about 90% of NC and FC. The exposure resulted lower than in the past, but this study highlights that PAHs exposure from the coke plant still poses a health risk for workers and the general population.

[Source apportionment of benzo(a)pyrene in Taranto and carcinogenic risk estimate in general population]. / Individuazione e caratterizzazione delle sorgenti di benzo(a)pirene nel comune di Taranto e stima del rischio cancerogeno associato all'esposizione della popolazione generale.

INTRODUCTION: In 2009 the limit value of benzo(a)pyrene (BaP) in ambient air of 1.0 ng/m3 has been exceeded in the urban district of Taranto near to the industrial area, where a several large plants are located, including an integrated cycle steel plant. OBJECTIVE: To identify emission sources and quantify relative contribution to the PAHs levels; to estimate health impact associated to PAHs exposure in general population. METHODS: Multivariate receptor models have been used. Concentration of PAHs measured in 4 location in Taranto in 2008-2009 have been analyzed. 5 different models estimated profiles of unknown sources and identified significant chemical species. To compute the lung cancer risk the WHO unit risk estimate for BaP (8.7 x 10(5) ng/m3) has been adopted. RESULTS: Models employed identify 3 to 4 emission sources. Estimated profiles have been compared with measured ones. Based on the average annual BaP level measured (1.3 ng/m3), 2 attributable cancer cases in the district Taranto population are estimated to result from a life-time exposure. CONCLUSIONS: Among different emissive sources, the analysis identifies theoretical sources whose profiles, compared with observed data, allow to identify dominant contributions to PAHs pollution and to design corrective actions to reduce environmental and health impact.

Searching for IgA nephropathy candidate genes: genetic studies combined with high throughput innovative investigations.

Idiopathic IgA Nephropathy (IgAN) is the most common biopsy-proven glomerulonephritis worldwide. All races with the exception of Blacks and Indians are involved. Families with two or more relatives affected by IgAN may be observed in 15-20% of pedigrees of IgAN patients. Genome wide linkage study has been considered the most promising approach to identify IgAN susceptibility genes. Therefore, some European investigators constituted the European IgAN Consortium which was initially funded by the European Union. Data from linkage analysis studies, family association studies and case-control association studies are reported. To date, the Consortium has identified two loci (located on chromosomes 4q26-31 and 17q12-22), in addition to the previous study which described the first IgAN locus on chromosome 6q22-23. The functional mapping of genes involved in the disease proceeds from the identification of susceptibility loci identified by linkage analysis (step 1) to the isolation of candidate genes within gene disease-susceptibility loci, after obtaining information by microarray analysis carried out on peripheral leukocytes and renal tissue samples (step 2). Then, the process will proceed from the design of RNA interferenceagents against selected genes (step 3) to the application of systematically tested effect of RNA agents on functional cellular assay (step 4). The above combined high-throughput technologies will give information on the pathogenic mechanisms of IgAN. In addition, these data may indicate potential targets for screening, prevention and early diagnosis of the disease and more appropriate and effective treatment.

The missing ApoE allele.

The human apoE gene (APOE, GenBank accession AF261279) shows a common polymorphism, with the three epsilon2, epsilon3 and epsilon4 alleles resulting from the haplotypes of two C-->T SNPs. However, whereas the three common T-T, T-C and C-C haplotypes corresponding to the epsilon2, epsilon3 and epsilon4 alleles are well known, the last C-T haplotype (GenBank accession AY077451), encoding a fourth apoE allele, has rarely been reported. We detected this fourth allele in a Caucasian patient with motor neuron disease (MND). According to the literature we refer to this allele as epsilon3r. Although several explanations may be proposed for its formation, the existence of this fourth allele is consistent with the evolutionary hypothesis generally accepted for the apoE alleles. The rarity and physiological role of epsilon3r remains to be explained, and requires further investigation.

[Biological monitoring in workers exposed to inorganic arsenic in a disused industrial plant in the area of Manfredonia]. / Monitoraggio biologico dell'esposizione professionale ad As inorganico in lavoratori di un impianto industriale dismesso nell'area di Manfredonia.

Inorganic arsenic and its methylated metabolities were measured in 108 spot urine samples obtained from the medical surveillance programme of workers exposed to inorganic Arsenic in July 2006. 15% of the samples showed levels higher than limit value of 35 microg/L (mean value 23,9 microg/L). After the improvement of the working conditions, in August-October 2006, we collected a urinary sample from each of the 108 workers enrolled. A questionnaire was also administrated, in order to investigate the influence of occupational and non occupational factors on the urinary arsenic excretion. The median value of urinary arsenic was 15,12 microg/L; among the 108 samples, 5% showed levels higher than limit value. A significant difference was observed in relation with sea-food consumption and aging stratification. In conclusion, we have described a significant reduction of urinary arsenic excretion between the two phases of biological monitoring, likely due to a proper hygienic work-related intervention.

Posttransplant recurrence of proteinuria in a case of focal segmental glomerulosclerosis associated with WT1 mutation.

Posttransplant recurrence of inherited focal segmental glomerulosclerosis (FSGS) is still an enigma owing to the evident paradox of the molecular origin of proteinuria. A young girl with FSGS for WT1 mutation (IVS9+4C>T) and Frasier syndrome received a renal transplant at the age of 11 years. After an initial good outcome with recovery of renal function, proteinuria re-appeared after 7 days and steadily increased up to a nephrotic range. Determination of plasma permeability activity showed concomitant high Palb (0.7). At this point, plasmapheresis was started and after nine cycles with 1500 mL exchange and albumin re-infusion, proteinuria decreased to normal range and is still normal after 3 years. This is the first description of posttransplant recurrence of proteinuria in Frasier syndrome that should be included in potential outcome of renal transplant in this category of patients. This observation confirms the concept that recurrence of proteinuria may occur in inherited forms of FSGS so far reported only for patients carrying NPHS2 mutations and reinforces the idea on multifactorial origin of the disease.

Biological monitoring and allergic sensitization in traffic police officers exposed to urban air pollution.

Urban air pollution is associated with an increased incidence of allergic respiratory diseases. The aim of this study is to assess the occupational exposure to urban pollution through biological monitoring of PAHs and CO airborne levels in 122 traffic wardens in Bari, Italy and to investigate sensitization to inhaled allergens in a subgroup of workers. After filling in a questionnaire on lifestyle habits and occupational history, a medical examination, spirometry were carried out and blood samples were taken; the measurement of exhaled CO and urinary 1-hydroxypyrene (1-HOP) was performed and data on the air quality of Bari Municipality were obtained. Specific IgE dosage and skin prick tests were done on 18 workers giving altered values of spirometry or anamnestic allergic symptoms. Urinary 1-HOP showed median levels of 0.1 microMol/Mol(creat) (range 0.02-6.68) and was not influenced by smoking habits, work tasks, area of the city and environmental levels of PM10. Exhaled CO, with median value of 1 ppm (range 0-27), was significantly higher in smokers than in non-smokers, while no other variable seemed to play a role in modifying the levels. Specific IgE production versus inhalant allergens was found in 6 cases. Positive skin prick test results were observed in 11 cases. Allergic rhinitis was diagnosed in 6 cases. At least one of the allergometric tests performed was positive in 61 percent of the subjects. In conclusion, our results suggest the importance of introducing allergic status evaluation in this class of workers, exposed to several urban air pollutants.