Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome

The aim of this study was to evaluate the presence of early vascular damage in young normal-weight women with polycystic ovary syndrome (PCOS).Thirty young normal-weight women with PCOS, who had no additional metabolic or cardiovascular diseases, and 30 healthy women (controls) matched for age and body mass index were studied. A complete hormonal assay was performed in each subject. Serum insulin and glucose levels were measured at baseline and after the oral glucose tolerance test. Plasma endothelin-1 levels and serum lipid profile were also assessed. The endothelial function was studied by flow-mediated dilation on the brachial artery, and arterial structure was evaluated by intima-media thickness measurement using Doppler ultrasound of both common carotid arteries.A significant (P < 0.05) difference in flow-mediated dilation (14.3 +/- 1.9% vs. 18.1 +/- 2.0% for PCOS patients and controls, respectively) and in intima-media thickness (0.53 +/- 0.09 mm vs. 0.39 +/- 0.08 mm for PCOS patients and controls, respectively) was found between PCOS and control subjects. Serum endothelin-1 levels were also significantly (P < 0.05) higher in PCOS patients compared with controls (1.1 +/- 0.4 pmol/liter vs. 0.5 +/- 0.2 pmol/liter for PCOS patients and controls, respectively).In conclusion, our data show that young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function

Crystal Structures of Human Pyridoxal Kinase in Complex with the Neurotoxins, Ginkgotoxin and Theophylline: Insights into Pyridoxal Kinase Inhibition

Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B6, pyridoxal 5′-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the B6 vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. We have performed structural and kinetic studies on hPL kinase with several potential inhibitors, including ginkgotoxin and theophylline. The structural studies show ginkgotoxin and theophylline bound at the substrate site, and are involved in similar protein interactions as the natural substrate, PL. Interestingly, the phosphorylated product of ginkgotoxin is also observed bound at the active site. This work provides insights into the molecular basis of hPL kinase inhibition and may provide a working hypothesis to quickly screen or identify neurotoxic drugs as potential hPL kinase inhibitors. Such adverse effects may be prevented by administration of an appropriate form of vitamin B6, or provide clues of how to modify these drugs to help reduce their hPL kinase inhibitory effects

Starving leukemia to induce differentiation

A new study shows that fasting induces the differentiation and elimination of some types of leukemia in mice, which implicates fasting or its mimetics as a novel strategy for the treatment of this disease

Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: The L-carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial

Objectives. This study was performed to evaluate the effects of l-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. Background. Carnitine is a physiologic compound that performs an essential role in myocardial energy production at the mitochondrial level. Myocardial carnitine deprivation occurs during ischemia, acute myocardial infarction and cardiac failure. Experimental studies have suggested that exogenous carnitine administration during these events has a beneficial effect on function. Methods. The l-Carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial was a randomized, double-blind, placebo-controlled, multicenter trial in which 472 patients with a first acute myocardial infarction and high quality two-dimensional echocardiograms received either placebo (239 patients) or l-carnitine (233 patients) within 24 h of onset of chest pain. Placebo or l-carnitine was given at a dose of 9 g/day intravenously for the first 5 days and then 6 g/day orally for the next 12 months. Left ventricular volumes and ejection fraction were evaluated on admission, at discharge from hospital and at 3, 6 and 12 months after acute myocardial infarction. Results. A significant attenuation of left ventricular dilation in the first year after acute myocardial infarction was observed in patients treated with l-carnitine compared with those receiving placebo. The percent increase in both end-diastolic and endsystolic volumes from admission to 3-, 6- and 12-mouth evaluation was significantly reduced in the l-carnitine group. No significant differences were observed in left ventricular ejection fraction changes over time in the two groups. Although not designed to demonstrate differences in clinical end points, the combined incidence of death and congestive heart failure after discharge was 14 (6%) in the l-carnitine treatment group versus 23 (9.6%) in the placebo group (p = NS). Incidence of ischemic events during follow-up was similar in the two groups of patients. Conclusions. l-Carnitine treatment initiated early after acute myocardial infarction and continued for 12 months can attenuate left ventricular dilation during the first year after an acute myocardial infarction, resulting in smaller left ventricular volumes at 3, 6 and 12 months after the emergent event

Variations in plant richness, biogeographical composition, and life forms along an elevational gradient in a mediterranean mountain

Despite the increasing interest in elevational patterns in biodiversity, few studies have investigated variations in life forms and biogeographical composition, especially in the Mediterranean biome. We investigated elevational patterns in species richness, biogeographical composition (chorotypes) and life forms (Raunkiaer classification) along an elevational gradient in a Mediterranean mountain (Central Italy). We found a general hump‐shaped pattern of species richness, which can be explained by harsher conditions at the lowest and highest elevations. This pattern is distinctly related to prevalence at mid elevations of species with European and Euro‐Asiatic distribution, which are favored by a temperate climate. Phanerophytes and geophytes (which are mainly associated with woods) were concentrated at mid elevations where woodlands prevail. Hemicrypto-phytes increased with elevation, consistently with their ability to cope with high altitude climatic conditions. Mediterranean species declined with elevation because they are negatively affected by decreasing temperatures. Chamaephytes showed a U‐shaped pattern, suggesting they are able to cope with arid and cold conditions at the extremes of the gradient. Endemics increased with elevation because of their association with mountainous areas as key places for endemism evolution. These results illustrate how elevational patterns in species richness, biogeographical composition and life forms are interrelated and demonstrate reciprocal insights for understanding current vegetation settings

Desogestrel down-regulates PHOX2B and its target genes in progesterone responsive neuroblastoma cells

The paired-like homeobox 2B gene (PHOX2B) encodes a key transcription factor that plays a role in the development of the autonomic nervous system and the neural structures involved in controlling breathing. In humans, PHOX2B over-expression plays a role in the pathogenesis of tumours arising from the sympathetic nervous system such as neuroblastomas, and heterozygous PHOX2B mutations cause Congenital Central Hypoventilation Syndrome (CCHS), a life-threatening neurocristopathy characterised by the defective autonomic control of breathing and involving altered CO2/H+ chemosensitivity. The recovery of CO2/H+ chemosensitivity and increased ventilation have been observed in two CCHS patients using the potent contraceptive progestin desogestrel. Given the central role of PHOX2B in the pathogenesis of CCHS, and the progesterone-mediated effects observed in the disease, we generated progesterone-responsive neuroblastoma cells, and evaluated the effects of 3-Ketodesogestrel (3-KDG), the biologically active metabolite of desogestrel, on the expression of PHOX2B and its target genes. Our findings demonstrate that, through progesterone nuclear receptor PR-B, 3-KDG down-regulates PHOX2B gene expression, by a post-transcriptional mechanism, and its target genes and open up the possibility that this mechanism may contribute to the positive effects observed in some CCHS patients

Swin-BSSeg: A Novel Swin Transformer-Enhanced Architecture for Accurate Ischemic Stroke Lesion Segmentation in MRI Images

Ischemic stroke, caused by obstructed cerebral blood flow, remains a leading cause of mortality and disability, necessitating precise magnetic resonance imaging (MRI)-based lesion detection. This paper proposes Swin-BSSeg (brain symmetry segmentation) algorithm, an enhanced version of the brain symmetry segmentation network (BSSNet), for improved stroke lesion segmentation. Swin-BSSeg integrates Swin Transformers to capture global context and long-range dependencies through a hierarchical attention mechanism. The encoder replaces traditional convolutions with depth-wise separable convolution (DWSC) blocks comprising three cascaded depth-wise convolutional layers for efficient feature extraction and parameter reduction. Feature transfer to the decoder is accomplished via concatenation operations. The decoder also employs DWSC blocks to reduce computational demands and incorporates attention-guided connections (AGC) to refine the contextual diversity—defined as model’s ability to capture varied and spatially distributed lesion features. The model was evaluated on the public datasets (Anatomical Tracings of Lesions after Stroke) and ISLES (Ischemic Stroke Lesion Segmentation), which achieved a Dice Coefficient of 0.842 and an accuracy of 0.87 on the ATLAS dataset, while a Dice Coefficient of 0.8049 and an accuracy of 0.84 on ISLES, outperforming BSSNet in contextual understanding and boundary precision. The improvements on the ATLAS dataset were statistically significant (p < 0.05), confirming the reliability of the proposed enhancements

Carabid community stability is enhanced by carabid diversity but reduced by aridity in Chinese steppes

Carabids (Coleoptera, Carabidae) are an important arthropod component of grassland ecosystems, where they are involved in many important ecosystem services. Grasslands are the most widespread ecosystems in China, where they are under increasing degradation that turn productive grasslands into desert. We studied the relationships between carabid community stability and various community parameters (richness, diversity, dominance, evenness, and proportion of the most dominant species) in three types of steppes characterized by a different degree of aridity (desert, typical and meadow) in northern China. Carabid community stability was lowest in the most arid environment (i.e. the desert steppe). In the less arid steppe (i.e. the meadow steppe) stability was correlated positively with richness, diversity, and equitability, and negatively with dominance and proportion of the most abundant species. This supports the diversity hypothesis (i.e. that high levels diversity lead to higher levels of stability, possibly by increasing niche complementation) and falsifies the mass ratio hypothesis (i.e. that ecosystem processes, and hence their stability, are strongly influenced by the most dominant species). Current transformation of productive grasslands into arid lands will reduce carabid community stability and this might compromise ecosystem functioning even at moderate levels of degradation, as observed in the typical steppe

Fine-scale vegetation characteristics drive insect ensemble structures in a desert ecosystem: The tenebrionid beetles (coleoptera: Tenebrionidae) inhabiting the ulan buh desert (inner mongolia, china)

In community ecology, ensembles are defined as phylogenetically bounded groups of species that use a similar set of resources within a community. Tenebrionids are a conspicuous faunal component of Asian deserts, but little is known about their community ecology. We investigated if tenebrionids associated with different plant species constitute ensembles with a different ecological structure. Sampling was done with pitfall traps placed beneath the most common plant species. Tenebrionid abundance patterns were modelled by fitting rank–abundance plots. The association between tenebrionid species and plant species was tested using contingency tables. Differences in ensemble diversity were investigated by diversity profiles. All ensembles were fitted by the geometric series model. Tenebrionid species were differently associated with different plant species. Diversity profiles indicate that different ensembles have different diversity patterns, because of differences in species relative abundance. Tenebrionids form different ensembles associated with the different dominant plant species. All these ensembles are, however, characterized by similar patterns of dominance, following the “niche pre-emption” model, and a steep decline in the diversity profiles. This indicates that similar environmental conditions lead to similar insect ensemble organization, although the most abundant species may vary, which suggests a role for microhabitat selection

Cardiovascular health in migrants: current status and issues for prevention. A collaborative multidisciplinary task force report.

OBJECTIVES: To review information on cardiovascular health and migration, to stress the attention of researchers that much needs to be done in the collection of sound data in Italy and to allow policy makers identifying this issue as an important public health concern. BACKGROUND: In Italy, the rate of immigrants in the total number of residents increased from 2.5% in 1990 to 7.4% in 2010, and currently exceeds 10% in regions such as Lombardia, Emilia Romagna and Toscana. METHODS: A consensus statement was developed by approaching relevant Italian national scientific societies involved in cardiovascular prevention. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. To obtain a widespread consensus, drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft was finally approved by scientific societies. RESULTS: In several western European countries, the prevalence of hypertension, diabetes, chronic kidney disease, obesity and metabolic syndrome was found to be higher among immigrants than in the native population. Although migrants are often initially healthier than non-migrant populations in their host countries, genetic factors, and changing environments with lifestyle changes, social exclusion and insufficient medical control may expose them to health challenges. Cultural reasons may also hamper both the dissemination of prevention strategies and migrant communication with healthcare providers. However, great diversity exists across and within different groups of migrants, making generalizations very difficult and many countries do not collect registry or survey data for migrant's health. CONCLUSIONS: In the present economic context, the European Union is placing great attention to improve data collection for migrant health and to support the implementation of specific prevention policies aimed at limiting the future burden of cardiovascular and renal disease, and the consequent load for health systems. Wider initiatives on the topic are awaited in Italy