Genomic and cytogenetic localization of the carotenoid genes in the aphid genome

Data published in the scientific literature suggests a possible link between chromosomal rearrangements involving autosomes 1 and 3 and the presence of red morphs in the peach-potato aphid Myzus persicae (Sulzer). In order to begin a study of this relationship, we analysed the genomic and chromosomal location of genes involved in carotenoid biosynthesis in M. persicae and the pea aphid, Acyrthosiphon pisum (Harris), since carotenoids are the basis of the colour in many aphid species. Genomic analysis identified a DNA sequence containing carotenoid genes in synteny between the 2 species. According to the results obtained using in situ PCR, carotenoid genes were located in a subterminal portion of autosome 1 in both species. The same localization has also been observed in the onion aphid Neotoxoptera formosana Takahashi that, as M. persicae and A. pisum, belongs to the tribe Macrosiphini, thereby suggesting a synteny of this chromosomal region in aphids. In situ PCR experiments performed on 2 M. persicae asexual lineages bearing heterozygous translocations involving autosomes 1 and 3 revealed that carotenoid genes were located within chromosomal portions involved in recurrent rearrangements. We also verified by bioinformatics analyses the presence of fragile sites that could explain these recurrent rearrangements in M. persicae

Characterization of Non-LTR Retrotransposable TRAS Elements in the Aphids Acyrthosiphon pisum and Myzus persicae (Aphididae, Hemiptera)

A non-LTR TRAS retrotransposon (identified as TRASAp1) has been amplified in the pea aphid Acyrthosiphon pisum and its presence has been assessed also in the peach potato aphid Myzus persicae. This TRAS element possesses 2 overlapping ORFs (a gag-ORF1 and a pol-ORF2 containing the reverse transcriptase and the endonuclease domains) that show a similarity ranging from 40% to 48% to proteins coded by other TRAS elements identified in insects (including the beetle Tribolium castaneum and the moth Bombyx mori). The study of the TRAS chromosomal insertion sites, performed by standard fluorescent in situ hybridization (FISH) and fiber FISH, showed that TRAS elements were located in a subtelomeric position, just before the telomeric (TTAGG)n repeats. In both the aphid species, TRAS elements were present at all termini of autosomes, but the 2 X chromosome telomeres show a clear-cut structural difference. Indeed, cromomycin A3 staining, together with FISH using a TRAS probe, revealed that TRAS signals only occur at the telomere opposite to the NOR-bearing one. Lastly, the analysis of the distribution of TRAS retrotransposons in a M. persicae strain possessing spontaneous fragmentations of the X chromosomes assessed that TRAS elements were not involved in the healing of de novo telomeres

Generalizability of Cardiovascular Safety Trials on SGLT2 Inhibitors to the Real World: Implications for Clinical Practice

Introduction: Following the US Food and Drug Administration (FDA) guidance on the evaluation of novel agents for the treatment of type 2 diabetes mellitus (T2DM), a number of cardiovascular outcomes safety trials (CVOTs) on sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been conducted. These trials show similarities in study design and definition of primary endpoints, but differ in their eligibility criteria. The aim of the present study was to investigate the generalizability of CVOTs on SGLT2i to Italian adults with T2DM; we estimated the proportions of this patient population who would be eligible for enrollment in EMPA-REG OUTCOME (empagliflozin), CANVAS (canagliflozin), DECLARE-TIMI 58 (dapagliflozin), and VERTIS-CV (ertugliflozin) studies. Methods: This observational, cross-sectional study was conducted in 222 Italian diabetes clinics. Data on 455,662 adult patients with T2DM seen during 2016 were analyzed against the published patient eligibility criteria for the four CVOTs. The current use of SGLT2i in potentially eligible patients was assessed. Results: Among the population identified, the proportion of patients meeting major eligibility criteria was 11.7% for EMPA-REG OUTCOME, 29.4% for CANVAS, 55.9% for DECLARE-TIMI 58, and 12.8% for VERTIS-CV. Of the patients eligible for these CVOTs, only a minority (range 4.4-6.8%) was actually prescribed an SGLT2i. Compared with patients in the CVOTs, eligible patients in the real world showed older age and longer diabetes duration, lower BMI and HbA1c levels, lower prevalence of established cardiovascular and cerebrovascular disease, and higher rates of microvascular complications and peripheral arterial disease. Conclusion: The percentage of patients potentially eligible for treatment with SGLT2i varies as a reflection of different eligibility criteria applied in the trials. A large number of patients that could benefit from SGLT2i in terms of not only cardiovascular protection but also renal protection do not receive the treatment

A performance score of the quality of inpatient diabetes care is a marker of clinical outcomes and suggests a cause-effect relationship between hypoglycaemia and the risk of in-hospital mortality

Aims: To build a tool to assess the management of inpatients with diabetes mellitus and to investigate its relationship, if any, with clinical outcomes. Materials and methods: A total of 678 patients from different settings, Internal Medicine (IMU, n = 255), General Surgery (GSU, n = 230) and Intensive Care (ICU, n = 193) Units, were enrolled. A work-flow of clinical care of diabetes was created according to guidelines. The workflow was divided into five different domains: (a) initial assessment; (b) glucose monitoring; (c) medical therapy; (d) consultancies; (e) discharge. Each domain was assessed by a performance score (PS), computed as the sum of the scores achieved in a set of indicators of clinical appropriateness, management and patient empowerment. Appropriate glucose goals were included as intermediate phenotypes. Clinical outcomes included: hypoglycaemia, survival rate and clinical conditions at discharge. Results: The total PS and those of initial assessment and glucose monitoring were significantly lower in GSU with respect to IMU and ICU (P <.0001). The glucose monitoring PS was associated with lower risk of hypoglycaemia (OR = 0.55; P <.0001), whereas both the PSs of glucose monitoring and medical therapy resulted associated with higher in-hospital survival only in the IMU ward (OR = 6.67 P =.001 and OR = 2.38 P =.03, respectively). Instrumental variable analysis with the aid of PS of glucose monitoring showed that hypoglycaemia may play a causal role in in-hospital mortality (P =.04). Conclusions: The quality of in-hospital care of diabetes may affect patient outcomes, including glucose control and the risk of hypoglycaemia, and through the latter it may influence the risk of in-hospital mortality

Case studies of automation in services

A full understanding of the technological complexity underlying robotics and automation is still lacking, most of all when focusing on the impacts on work in services. By means of a qualitative analysis based on over 50 interviews to HR managers, IT technicians, workers and trade union delegates, this work provides evidence on the main changes occurring at shopfloor level in selected Italian companies having adopted technological artefacts potentially affecting labour tasks by automating processes. The analysis of interviews complemented with visits to the companies and desk research on business documents highlights that so far labour displacement due to the adoption of automation technologies is not yet in place, while tasks and organizational reconfiguration appear more widespread. Major heterogeneity applies across plants due to the final product/service produced, the techno-organizational capabilities of the firm and the type of strategic orientation versus technological adoption. These elements also affect drivers and barriers to technological adoption. Overall, the analysis confirms the complexity in automating presumably low-value-added phases: human labour remains crucial in conducting activities that require flexibility, adaptability and reconfiguration of physical tasks. Further, human agency and worker representation, in particular the role of trade unions, are almost disregarded and not considered by the firms when deciding to introduce a new technology

Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study

Background: The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. Methods: The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. Results: Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. Conclusions: A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care

Case Studies of Automation in Services. A workplace analysis of logistics, cleaning and health sectors in Italy

A full understanding of the technological complexity underlying robotics and automation is still lacking, most of all when focusing on the impacts on work in services. By means of a qualitative analysis relying on the administration of more than 50 interviews to HR managers, IT technicians, workers and trade union delegates, this work provides evidence on the main changes occurring at shopfloor level in selected Italian companies having adopted technological artefacts potentially affecting labour tasks by automating processes. The analysis of interviews complemented with visits to the companies and desk research on business documents highlights that so far labour displacement due to the adoption of automation technologies is not yet in place, while tasks and organizational reconfiguration appear more widespread. Major heterogeneity applies across plants due to the final product/service produced, the techno-organizational capabilities of the firm and the type of strategic orientation versus technological adoption. These elements also affect drivers and barriers to technological adoption. Overall, the analysis confirms the complexity in automating presumably low-valueadded phases: human labour remains crucial in conducting activities that require flexibility, adaptability and reconfiguration of physical tasks. Further, human agency and worker representation, in particular the role of trade unions, are almost disregarded and not considered by the firms when deciding to introduce a new technology

The AMD ANNALS: A continuous initiative for the improvement of type 2 diabetes care

Aims: Since 2006, the Italian AMD (Associations of Medical Diabetologists) Annals Initiative promoted a continuous monitoring of the quality of diabetes care, that was effective in improving process, treatment and outcome indicators through a periodic assessment of standardized measures. Here, we show the 2022 AMD Annals data on type 2 diabetes (T2D).Methods: A network involving similar to 1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic clinical records, by a standardized software. Process, treatment and outcome indicators, and a vali-dated score of overall care, the Q-score, were evaluated.Results: 295 centers provided the annual sample of 502,747 T2D patients. Overall, HbA1c value 25.Conclusions: The 2022 AMD Annals data show an improvement in the use of innovative drugs and in the overall quality of T2D care in everyday clinical practice. However, additional efforts are needed to reach the recom-mended targets for HbA1c and major CVD risk factors

Xenoestrogenic activity in blood of European and Inuit populations.

Human exposure to persistent organic pollutants (POPs) is ubiquitous and found in all individuals. Studies have documented endocrine disrupting effects and impact on reproduction. The aim of the present study was to compare the level of xenoestrogenic activity in serum of groups with varying POP exposure, and to evaluate correlations to the POP biomarkers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE). No strong consistent association between xenoestrogenic net activity and the two POP markers was found. The results showed that the selected POP markers alone can not predict the integrated xenoestrogenic serum activity. Correlations to the POP markers were found at the extreme edge; the Inuit's and Warsaw study groups eliciting high frequency of samples with ER antagonistic and agonistic activity, respectively. We suggest that the variation in xenoestrogenic serum activity reflects differences in POP exposure mixture, genetic factors and/or life style factors

Impact of PCB and p,p'-DDE contaminants on human sperm Y : X chromosome ratio: Studies in three European populations and the inuit population in Greenland

Recent studies indicate that persistent organohalogen pollutants (POPs) may contribute to sex ratio changes in offspring of exposed populations. Our aim in the present study was to investigate whether exposure to 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153) and dichlorodiphenyldichloroethene (pp'-DDE) affects sperm Y:X chromosome distribution. SUBJECTS AND METHODS: We obtained semen and blood for analysis of PCB-153 and pp'-DDE levels from 547 men from Sweden, Greenland, Poland (Warsaw), and Ukraine (Kharkiv), with regionally different levels of POP exposure. The proportion of Y- and X-chromosome-bearing sperm in the semen samples was determined by two-color fluorescence in situ hybridization analysis. RESULTS: Swedish and Greenlandic men had on average significantly higher proportions of Y sperm (in both cohorts, 51.2%) and correspondingly higher lipid-adjusted concentrations of PCB-153 (260 ng/g and 350 ng/g, respectively) compared with men from Warsaw (50.3% and 22 ng/g) and Kharkiv (50.7% and 54 ng/g). In the Swedish cohort, log-transformed PCB- 153 and log-transformed pp'-DDE variables were significantly positively associated with Y-chromosome fractions (p-values 0.04 and < 0.001, respectively). On the contrary, in the Polish cohort PCB-153 correlated negatively with the proportion of Y-bearing fraction of spermatozoa (p = 0.008). CONCLUSIONS: The present study indicates that POP exposure might be involved in changing the proportion of ejaculated Y-bearing spermatozoa in human populations. Intercountry differences, with different exposure situations and doses, may contribute to varying Y:X chromosome ratios