Heatwave Definition and Impact on Cardiovascular Health: A Systematic Review

Objectives: We aimed to analyze recent literature on heat effects on cardiovascular morbidity and mortality, focusing on the adopted heat definitions and their eventual impact on the results of the analysis.Methods: The search was performed on PubMed, ScienceDirect, and Scopus databases: 54 articles, published between January 2018 and September 2022, were selected as relevant.Results: In total, 21 different combinations of criteria were found for defining heat, 12 of which were based on air temperature, while the others combined it with other meteorological factors. By a simulation study, we showed how such complex indices could result in different values at reference conditions depending on temperature. Heat thresholds, mostly set using percentile or absolute values of the index, were applied to compare the risk of a cardiovascular health event in heat days with the respective risk in non-heat days. The larger threshold's deviation from the mean annual temperature, as well as higher temperature thresholds within the same study location, led to stronger negative effects.Conclusion: To better analyze trends in the characteristics of heatwaves, and their impact on cardiovascular health, an international harmonization effort to define a common standard is recommendable

A lymphofollicular microenvironment is required for pathological prion protein deposition in chronically inflamed tissues from scrapie-affected sheep

In sheep scrapie, pathological prion protein (PrPSc) deposition occurs in the lymphoreticular and central nervous systems. We investigated PrPSc distribution in scrapie- affected sheep showing simultaneous evidence of chronic lymphofollicular, lymphoproliferative/non-lymphofollicular,and/or granulomatous inflammations in their mammary gland, lung, and ileum. To do this, PrPSc detection was carried out via immunohistochemistry and Western Blotting techniques, as well as through inflammatory cell immunophenotyping. Expression studies of gene coding for biological factors modulating the host’s inflammatory response were also carried out. We demonstrated that ectopic PrPSc deposition occurs exclusively in the context of lymphofollicular inflammatory sites, inside newly formed and well-organized lymphoid follicles harboring follicular dendritic cells. On the contrary, no PrPSc deposition was detected in granulomas, even when they were closely located to newly formed lymphoid follicles. A significantly more consistent expression of lymphotoxin α and β mRNA was detected in lymphofollicular inflammation compared to the other two types, with lymphotoxin α and β signaling new lymphoid follicles’ formation and, likely, the occurrence of ectopic PrPSc deposition inside them. Our findings suggest that, in sheep co-affected by scrapie and chronic inflammatory conditions, only newly formed lymphoid follicles provide a suitable micro-environment that supports the scrapie agent’s replication in inflammatory sites, with an increased risk of prion shedding through body secretions/excretions.[...

Haplotype Affinities Resolve a Major Component of Goat (Capra hircus) MtDNA D-Loop Diversity and Reveal Specific Features of the Sardinian Stock

Goat mtDNA haplogroup A is a poorly resolved lineage absorbing most of the overall diversity and is found in locations as distant as Eastern Asia and Southern Africa. Its phylogenetic dissection would cast light on an important portion of the spread of goat breeding. The aims of this work were 1) to provide an operational definition of meaningful mtDNA units within haplogroup A, 2) to investigate the mechanisms underlying the maintenance of diversity by considering the modes of selection operated by breeders and 3) to identify the peculiarities of Sardinian mtDNA types. We sequenced the mtDNA D-loop in a large sample of animals (1,591) which represents a non-trivial quota of the entire goat population of Sardinia. We found that Sardinia mirrors a large quota of mtDNA diversity of Western Eurasia in the number of variable sites, their mutational pattern and allele frequency. By using Bayesian analysis, a distance-based tree and a network analysis, we recognized demographically coherent groups of sequences identified by particular subsets of the variable positions. The results showed that this assignment system could be reproduced in other studies, capturing the greatest part of haplotype diversity

Microsatellite diversity of the Nordic type of goats in relation to breed conservation: how relevant is pure ancestry?

In the last decades, several endangered breeds of livestock species have been re-established effectively. However, the successful revival of the Dutch and Danish Landrace goats involved crossing with exotic breeds and the ancestry of the current populations is therefore not clear. We have generated genotypes for 27 FAO-recommended microsatellites of these landraces and three phenotypically similar Nordic-type landraces and compared these breeds with central European, Mediterranean and south-west Asian goats. We found decreasing levels of genetic diversity with increasing distance from the south-west Asian domestication site with a south-east-to-north-west cline that is clearly steeper than the Mediterranean east-to-west cline. In terms of genetic diversity, the Dutch Landrace comes next to the isolated Icelandic breed, which has an extremely low diversity. The Norwegian coastal goat and the Finnish and Icelandic landraces are clearly related. It appears that by a combination of mixed origin and a population bottleneck, the Dutch and Danish Land-races are separated from the other breeds. However, the current Dutch and Danish populations with the multicoloured and long-horned appearance effectively substitute for the original breed, illustrating that for conservation of cultural heritage, the phenotype of a breed is more relevant than pure ancestry and the genetic diversity of the original breed. More in general, we propose that for conservation, the retention of genetic diversity of an original breed and of the visual phenotype by which the breed is recognized and defined needs to be considered separately

Effects of angiotensin II on insulin receptor binding and mRNA levels in normal and diabetic rats

6Both the density and level of mRNA encoding insulin receptors in the kidney are inversely related to the dietary sodium content, suggesting a feedback mechanism that limits the insulin-induced sodium retention when extracellular fluid volume is expanded. Because angiotensin II affects tissue sensitivity to insulin in humans, we investigated whether angiotensin II affects insulin receptor binding and mRNA levels in the kidney, liver, and renal arteries of normal rats and rats with streptozotocin-induced diabetes mellitus. Non-diabetic and diabetic rats were infused for 7 days with either vehicle or angiotensin II at a rate of 200 ng . kg(-1) . min(-1). In a separate experiment, normal rats were treated with an angiotensin converting enzyme inhibitor (captopril, 100 mg/dl in the drinking water) or vehicle for 7 days. Regional analysis of insulin receptor binding in the kidney and renal arteries was performed by an in situ technique using computerized microdensitometry and emulsion autoradiography. Insulin receptor mRNA levels were determined in renal and hepatic tissue by Northern blot hybridization and normalized with 28S rRNA. No differences in blood pressure were observed among diabetic and non-diabetic rats infused with either vehicle or angiotensin II, whereas captopril-treated rats had significantly lower blood pressure levels than their respective controls. Angiotensin II significantly decreased plasma renin concentration in both non-diabetic and diabetic rats. Insulin receptor number was significantly greater in the renal cortex of diabetic rats than in non-diabetics, whereas no significant differences were found in the outer medulla, inner medulla, or renal arteries. Angiotensin II infusion did not affect either the number or affinity of insulin receptors in any of the renal regions studied. Insulin receptor mRNA levels were significantly greater in the kidney and liver of diabetic rats than in non-diabetics and were not: affected by angiotensin II infusion. Similar to angiotensin II infusion, captopril treatment did not affect either renal insulin receptor binding or mRNA levels. Thus, diabetic rats have increased insulin receptor binding and mRNA levels in comparison to non-diabetic rats. Angiotensin II infusion and captopril treatment do not affect insulin receptor binding and mRNA levels in the kidney, arguing against a role for this peptide in the modulation of renal sensitivity to insulin.nonenoneSechi L; Griffin CA; Zingaro L; Valentin JP; Bartoli E; Schambelan MSechi, Leonardo Alberto; Griffin, Ca; Zingaro, L; Valentin, Jp; Bartoli, E; Schambelan, M

The Impact of COVID-19 on Lombardy Region ST-Elevation Myocardial Infarction Emergency Medical System Network—A Three-Year Study

Objectives: The COVID-19 pandemic had a significant impact on emergency medical systems (EMS). Regarding the ST-elevation myocardial infarction (STEMI) dependent time network, however, there is little evidence linked to the post-pandemic phase regarding this issue. Such information could prove to be of pivotal importance regarding STEMI clinical management, especially pre-hospital clinical protocols such as fibrinolysis. Methods: A retrospective observational cohort study of all STEMI rescues recorded in the Lombardy EMS registry from the 1st of January 2019 to the 30th of December 2021. Results: Regarding the number of STEMI diagnoses, March 2020 (first pandemic wave in Italy) saw a reduction compared to March 2019 (OR 0.76 [0.60–0.93], p = 0.011). The average time of the entire mission increased to 63.1 min in 2021, reaching 64.7 min in 2020, compared with 57.7 min in 2019. The number of HUBs for STEMI patients saw a reduction, falling from 52 HUBs in the pre-pandemic phase to 13 HUBs during the first wave. Conclusions: During the pandemic phase, there was an increase in the transportation times of STEMI patients from home to the hospital. Such changes did not alter the clinical approach in the out-of-hospital phase. Indeed, the implementation of fibrinolysis was not required

<i>Mycobacterium tuberculosis</i> lipoarabinomannan antibodies are associated to rheumatoid arthritis in Sardinian patients

Little is known regarding the environmental factors at play in igniting rheumatoid arthritis (RA) autoimmunity, although an association between Mycobacteria and RA has been documented. This pilot study focused on examining a possible involvement of Mycobacterium tuberculosis (MTB) and Mycobacterium avium ss. paratuberculosis (MAP) in RA. We measured out the serum levels of IgGantibody against different mycobacterial antigens in Sardinian patients and controls, by an enzyme-linked immunosorbent assay. The population study was composed of 61 RA patients under different therapies and 52 healthy controls, whereas the antigens tested were MTB lipoarabinomannan (ManLAM), MAP heath shock protein 70, and MAP protein tyrosine phosphatase. The frequencies of anti-ManLAM antibodies were higher in the RA group (23 %) compared to the healthy controls (5.7 %) (AUC = 0.7; p &#60; 0.0001), whereas serum reactivity to MAP antigens was not observed. ManLAM antigen was also detected in the plasma of three RA patients (which were anti-ManLAM antibody positive) by Western blot analysis using anti-Man-LAM monoclonal antibodies. The data produced corroborate the hypothesis of a potential association between MTB ManLAM and RA disease, but so far, further studies are necessary to understand its role in RA pathogenesis

The muscle relaxant thiocolchicoside is an antagonist of GABA(A) receptor function in the central nervous system

Thiocolchicoside (TCC) is used clinically for its muscle relaxant, anti-inflammatory, and analgesic properties, and it has been shown to interact with gamma-aminobutyric acid (GABA) type A receptors (GABA(A)Rs) and strychnine-sensitive glycine receptors in the rat central nervous system. In contrast to a proposed agonistic action at these two types of inhibitory receptors, pharmacological evidence has shown that, under certain conditions, TCC manifests convulsant activity in animals and humans. We now show that the phasic and tonic GABA(A)R-mediated currents recorded from Purkinje cells and granule neurons, respectively, in parasagittal cerebellar slices from adult mate rats were inhibited by TCC in a concentration-dependent manner. The median inhibitory concentrations of TCC for these effects were similar to 0.15 and similar to 0.9 mu M, respectively. TCC did not potentiate GABA(B)R-mediated currents in hippocampal slices, suggesting that its muscle relaxant action is not mediated by GABA(B)Rs. Intraperitoneal injection of TCC in rats either alone or in combination with negative modulators of GABAergic transmission revealed convulsant and proconvulsant actions of this drug. Our data, consistent with clinical observations of the epileptogenic effect of this compound, suggest that TCC is a potent competitive antagonist of GABA(A)R functio