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* Context.--Perinatal death is an increasingly important problem as the coronavirus disease 2019 (COVID-19) pandemic continues, but the mechanism of death has been unclear. Objective.--To evaluate the role of the placenta in causing stillbirth and neonatal death following maternal infection with COVID-19 and confirmed placental positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Design.--Case-based retrospective clinicopathologic analysis by a multinational group of 44 perinatal specialists from 12 countries of placental and autopsy pathology findings from 64 stillborns and 4 neonatal deaths having placentas testing positive for SARS-CoV-2 following delivery to mothers with COVID-19. Results.--Of the 3 findings constituting SARS-CoV-2 placentitis, all 68 placentas had increased fibrin deposition and villous trophoblast necrosis and 66 had chronic histiocytic intervillositis. Sixty-three placentas had massive perivillous fibrin deposition. Severe destructive placental disease from SARS-CoV-2 placentitis averaged 77.7% tissue involvement. Other findings included multiple intervillous thrombi (37%; 25 of 68) and chronic villitis (32%; 22 of 68). The majority (19; 63%) of the 30 autopsies revealed no significant fetal abnormalities except for intrauterine hypoxia and asphyxia. Among all 68 cases, SARS-CoV-2 was detected from a body specimen in 16 of 28 cases tested, most frequently from nasopharyngeal swabs. Four autopsied stillborns had SARS-CoV-2 identified in internal organs. Conclusions.--The pathology abnormalities composing SARS-CoV-2 placentitis cause widespread and severe placental destruction resulting in placental malperfusion and insufficiency. In these cases, intrauterine and perinatal death likely results directly from placental insufficiency and fetal hypoxic-ischemic injury. There was no evidence that SARS-CoV-2 involvement of the fetus had a role in causing these deaths., The emergence of new viral diseases has always created anxiety among persons at risk for infection, but perhaps this is most true for pregnant women, who fear not only for [...]

BACKGROUND: Bullous pemphigoid (BP) is a rare autoimmune blistering disease predominantly affecting the elderly population. OBJECTIVES: The present study aims to identify clinical factors that may influence outcomes of BP, including skin phenotype, serology, mucosal involvement, pruritus, and triggers. METHODS: A retrospective analysis was conducted on 70 cases with BP registered from January 2019 to December 2022. The Bullous Pemphigoid Disease Activity Index (BPDAI) score was used to assess disease intensity. The BPDAI-Pruritus score and a modified Brest questionnaire were used to document pruritus. Anti-BP180 and anti-BP230 autoantibodies were regularly recorded. Peripheral blood eosinophil counts were documented during flare-up and remission phases of BP. RESULTS. Of the cases, 81.4% were identified with bullous BP, 12.9% with nonbullous BP and 5.7% with localized BP. Oral involvement was documented in 17.1% of cases. Increased peripheral eosinophilia was prominent in the nonbullous phenotype and returned to normal level during remission in both phenotypes. CONCLUSION: The outcomes of BP depended on the disease phenotype and trigger types. Bullous BP showed more intense disease activity, while nonbullous BP demonstrated more intense pruritus. BP associated with diabetes mellitus (DM) or psoriasis manifested as a more severe disease, predominantly with the bullous phenotype and pruritus, compared to cases without comorbidities. New triggers, including SARS-CoV-2 infection and vaccination, were documented. [ABSTRACT FROM AUTHOR]

Introduction MicroRNAs (miRNAs) represent small (22-24 nucleotides long) non-coding RNA molecules that regulate the expression of various target genes by hybridization to 3' untranslated region (3'UTR) of target mRNA (Small [...], Radiotherapy is the most commonly used methodology to treat oncological disease, one of the most widespread causes of death worldwide. Oncological patients cured by radiotherapy applied to the mediastinal area have been shown to suffer from cardiovascular disease. The increase in the prevalence of radiation- induced heart disease has emphasized the need to seek new therapeutic targets to mitigate the negative impact of radiation on the heart. In this regard, microRNAs (miRNAs) have received considerable interest. miRNAs regulate post- transcriptional gene expression by their ability to target various mRNA sequences because of their imperfect pairing with mRNAs. It has been recognized that miRNAs modulate a diverse spectrum of cardiac functions with developmental, pathophysiological, and clinical implications. This makes them promising potential targets for diagnosis and treatment. This review summarizes the recent findings about the possible involvement of miRNAs in radiation-induced heart disease and their potential use as diagnostic or treatment targets in this respect. Key words: free radicals, inflammation, microRNA, oxidative stress, radiation- induced heart disease. La radiotherapie constitue la modalite la plus courante pour traiter le cancer, l'une des causes les plus repandues de deces a l'echelle mondiale. On a montre que les patients cancereux gueris par la radiotherapie appliquee a la region mediastinale souffrent de maladies cardiovasculaires. L'augmentation de la prevalence de la maladie cardiaque entrainee par la radiotherapie a mis de l'emphase sur la necessite de chercher de nouvelles cibles therapeutiques pour mitiger l'incidence negative des rayonnements sur le creur. A cet egard, les microARN (miARN) ont recu une attention considerable. Les miARN assurent la regulation de l'expression post-transcriptionnelle des genes, par leur capacite de cibler diverses sequences d'ARNm en raison de leur appariement imparfait avec les ARNm. On s'est rendu compte que les miARN assurent la modulation d'un spectre diversifie de fonctions cardiaques, avec des implications sur le plan du developpement, de la physiopathologie et de la clinique. Cela en fait des cibles potentielles prometteuses en vue du diagnostic et du traitement. Cet article de synthese resume les resultats recents quant a la participation eventuelle des miARN dans la maladie cardiaque entrainee par les rayonnements et leur utilisation potentielle comme cibles de diagnostic et de traitement dans ce contexte. [Traduit par la Redaction] Mots-cles: radicaux libres, inflammation, microARN, stress oxydatif, maladie cardiaque entrainee par des rayonnements.

Introduction Treatment of oncological patients often requires radiation therapy (RT). Despite modern radiotherapy techniques, in some cases irradiation of tumors inevitably involves also exposure of normal tissues that causes undesired [...], Irradiation of normal tissues leads to acute increase in reactive oxygen/nitrogen species that serve as intra- and inter-cellular signaling to alter cell and tissue function. In the case of chest irradiation, it can affect the heart, blood vessels, and lungs, with consequent tissue remodelation and adverse side effects and symptoms. This complex process is orchestrated by a large number of interacting molecular signals, including cytokines, chemokines, and growth factors. Inflammation, endothelial cell dysfunction, thrombogenesis, organ dysfunction, and ultimate failing of the heart occur as a pathological entity--"radiation-induced heart disease" (RIHD) that is major source of morbidity and mortality. The purpose of this review is to bring insights into the basic mechanisms of RIHD that may lead to the identification of targets for intervention in the radiotherapy side effect. Studies of authors also provide knowledge about how to select targeted drugs or biological molecules to modify the progression of radiation damage in the heart. New prospective studies are needed to validate that assessed factors and changes are useful as early markers of cardiac damage. Key words: radiation induced heart disease, ischemia, apoptosis, adaptation, markers. L&apos;irradiation de tissus normaux mene a une augmentation aigue de la formation de derives reactifs de l&apos;oxygene ou de l&apos;azote, qui agissent en tant que voies de signalisation intra-et extra-cellulaires pour modifier le fonctionnement des cellules et des tissus. Dans le cas de l&apos;irradiation du thorax, cela peut affecter le coeur, les vaisseaux sanguins et les poumons, avec un remodelage consecutif des tissus ainsi que des effets indesirables et des symptomes. Ce processus complexe est orchestre par l&apos;interaction d&apos;un grand nombre de signaux moleculaires, y compris des cytokines, des chimiokines et des facteurs de croissance. L&apos;inflammation, le dysfonctionnement des cellules endotheliales, la thrombogenese, le dysfonctionnement des organes et enfin l&apos;insuffisance cardiaque peuvent survenir comme une entite, la << cardiopathie post-radique >> (CPR), source majeure de morbidite et de mortalite. L&apos;article de synthese a pour objectif d&apos;apporter des perspectives pour les modes d&apos;action a la base de la CPR qui pourraient mener a l&apos;etablissement de cibles pour des interventions contre les effets indesirables de la radiotherapie. Les etudes d&apos;auteurs permettent aussi d&apos;obtenir des connaissances sur la maniere de selectionner des medicaments ou des molecules biologiques cibles en vue de modifier l&apos;evolution des dommages cardiaques causes par les rayonnements. De nouvelles etudes prospectives sont necessaires pour valider que les facteurs et les changements evalues sont utiles comme marqueurs precoces de dommages cardiaques. [Traduit par la Redaction] Mots-cles: cardiopathie post-radique, ischemie, apoptose, adaptation, marqueurs.

Innervation of cancerous tissue represents an important pathway enabling the nervous system to influence the processes associated with the initiation, progression, and metastasis of a neoplastic process. In the context of prostate cancer, several papers report the presence of innervation and its modulating effect on the cancer prognosis. However, most of the data are experimental, with limited information on human prostate cancer innervation. Morphometric analysis of archival prostate specimen immunohistochemistry with neural markers PGP9.5 and S100 showed a significant decrease of nerve density in the prostate cancer (n=44) compared to the normal prostate tissue (n=18) and benign prostatic hyperplasia (n=28). Sympathetic nerves were detected with TH, parasympathetic with VAChT, and sensory nerves with SP and CGRP protein detection. Dual immunofluorescence revealed numerous sympathetic nerves in normal prostate and benign prostatic hyperplasia, especially in the peripheral parts. Only a few parasympathetic nerves were found between the glands and in the peripheral parts of the prostate and benign hyperplasia. Sporadic positivity for sensory innervation was present only in approximately 1/10 of nerve fibers, especially in the larger nerves. The pattern of innervation in prostate cancer was analogous to that in normal prostate gland and benign prostatic hyperplasia but there was a significantly lower amount of all nerve types, especially in high-grade carcinoma cases. Although not significant, there was a tendency of decreasing innervation density with increasing Gleason score. Regarding the low density of nerves in prostate carcinoma, the significantly lower PCNA counts in nerves of the cancer specimens cannot be ascribed to lower proliferation activity. Our data confirmed the lower nerve density in the prostate cancer compared to the benign prostate tissue. We could not approve an increased nerve proliferation activity in prostate cancer. All nerve types, most the sympathetic, less the parasympathetic, and the sensory nerves, are present in prostate cancer. The highest nerve density at the periphery of the cancer tissue implies this to be the result of an expansive tumor growth. It is evident that the results of experimental prostate cancer models can be applied to human pathology only to a certain extent. The relation between the range of innervation and the biology of prostate cancer is very complex and will require more detailed information to be applied in therapeutic solutions. [ABSTRACT FROM AUTHOR]

Hypoxic pulmonary vascular remodeling in rats is associated with increased polyamine transport in pulmonary artery smooth muscle cells (PASMCs). We therefore defined constitutive and hypoxia-induced polyamine transport properties of rat cultured PASMCs and determined the impact of polyamine transport blockade on hypoxia-induced accumulation of p38 MAP kinase. PASMCs exhibited polyamine transport pathways that were characterized by Michaelis-Menten kinetics. RNA synthesis inhibition attenuated while inhibition of protein synthesis increased polyamine uptake, thus suggesting regulation by ornithine decarboxylase-antizyme. The presence of two transporters with overlapping selectivities, one for putrescine and another for all three polyamines, was inferred by cross-competition studies and by findings that only putrescine uptake was sodium dependent and that hypoxia caused a selective, time-dependent induction of putrescine transport. The pathophysiological significance of augmented putrescine import was suggested by the observation that polyamine transport inhibition suppressed hypoxia-induced p38 MAP kinase phosphorylation. These results indicate that rat PASMCs express two polyamine transporters and that a specific increase in the putrescine uptake pathway is necessary for hypoxia-induced activation of p38 MAP kinase. pulmonary hypertension; vascular smooth muscle; hypoxia; pulmonary artery smooth muscle cells; mitogen-activated protein

In rat lung and cultured lung vascular cells, hypoxia decreases ornithine decarboxylase (ODC) activity and increases polyamine import. In this study, we used rat cultured pulmonary artery endothelial cells to explore the mechanism of hypoxia-induced reduction in ODC activity and determined whether this event was functionally related to the increase in polyamine import. Two strategies known to suppress proteasome-mediated ODC degradation, lactacystin treatment and use of cells expressing a truncated ODC incapable of interacting with the proteasome, prevented the hypoxia-induced decrease in ODC activity. Interestingly, though, cellular abundance of the 24-kDa antizyme, a known physiological accelerator of ODC degradation, was not increased by hypoxia. These observations suggest that an antizyme-independent ODC degradation pathway contributes to hypoxia-induced reductions of ODC activity. When reductions in ODC activity in hypoxia were prevented by the proteasome inhibitor strategies, hypoxia failed to increase polyamine transport. The induction of polyamine transport in hypoxic pulmonary artery endothelial cells thus seems to require decreased ODC activity as an initiating event. pulmonary endothelial cells; pulmonary hypertension; polyamines