New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study.

PURPOSE: Many questions concerning Turner syndrome (TS) remain unresolved, such as the long-term complications and, therefore, the optimal care setting for adults. The primary aim of this long-term cohort study was to estimate the incidence of comorbid conditions along the life course. METHODS: A total of 160 Italian patients with TS diagnosed from 1967 to 2010 were regularly and structurally monitored from the diagnosis to December 2019 at the University Hospital of Bologna using a structured multidisciplinary monitoring protocol. RESULTS: The study cohort was followed up for a median of 27 years (IQR 12-42). Autoimmune diseases were the comorbid condition with the highest incidence (61.2%), followed by osteoporosis and hypertension (23.8%), type 2 diabetes (16.2%) and tumours (15.1%). Median age of onset ranged from 22 years for autoimmune diseases to 39 years for type 2 diabetes. Malignant tumours were the most prominent type of neoplasm, with a cumulative incidence of 11.9%. Papillary thyroid carcinoma was the most common form of cancer, followed by skin cancer and cancer of the central nervous system. Only one major cardiovascular event (acute aortic dissection) was observed during follow-up. No cases of ischaemic heart disease, heart failure, stroke or death were recorded. CONCLUSIONS: This cohort study confirms the need for continuous, structured and multidisciplinary lifelong monitoring of TS, thus ensuring the early diagnosis of important comorbid conditions, including cancer, and their appropriate and timely treatment. In addition, these data highlight the need for the increased surveillance of specific types of cancer in TS, including thyroid carcinoma.

A mathematical model of cerebral blood flow chemical regulation--Part I: Diffusion processes.

This paper proposes a mathematical model which describes the production and diffusion of vasoactive chemical factors involved in oxygen-dependent cerebral blood flow (CBF) regulation in the rat. Partial differential equations describing the relations between input and output variables have been replaced with simpler ordinary differential equations by using mathematical approximations of the hyperbolic functions in the Laplace transform domain. This model is composed of two submodels. In the first, oxygen transport from capillary blood to cerebral tissue is analyzed to link changes in mean tissue oxygen pressure with CBF and arterial oxygen concentration changes. The second submodel presents equations describing the production of vasoactive metabolites by cerebral parenchyma, due to a lack of oxygen, and their diffusion towards pial perivascular space. These equations have been used to simulate the time dynamics of mean tissue PO2, perivascular adenosine concentration, and perivascular pH to changes in CBF. The present simulation points out that the time delay introduced by diffusion processes is negligible if compared with the other time constants of the system under study. In a subsequent work the same equations will be included in a model of the cerebral vascular bed to clarify the metabolite role in CBF regulation.

A mathematical model of cerebral blood flow chemical regulation--Part II: Reactivity of cerebral vascular bed.

In the present paper an original mathematical model of the chemical oxygen-dependent cerebral blood flow (CBF) regulation in the rat is proposed. Taking into account recent experimental works, the model assumes that oxygen acts on cerebral vessels through an indirect mechanism, mediated by the release of two metabolic substances (adenosine and H+) from tissue, and that any change in perivascular concentration of these substances affects the diameter of both the medium and small pial arteries as well as of intracerebral arterioles. The model is composed of several submodels, each closely related to a different physiological event. mathematical equations, which describe the reaction of the vasoactive portion of the cerebral vascular bed, are reported in detail and justified. The model permits the simulation of the role played by chemical factors in the control of CBF under many different physiological and pathological conditions in an attempt to clarify their relevance. Several events associated with an alteration in oxygen supply to tissue (auto-regulation to changes in arterial and venous pressure, reactive hyperemia following on cerebral ischemia, arterial hypoxia) have been simulated with the model. The results suggest that chemical factors, adenosine and H+, play a significant but not exclusive role in the regulation of the cerebral vascular bed. The action of other mechanisms (which are probably neurogenic) must be hypothesized to explain completely the CBF changes occurring in vivo.