Sociodemographic profile, health-related behaviours and experiences of healthcare access in Italian transgender and gender diverse adult population.

PURPOSE: Information on the general health of transgender and gender diverse (TGD) individuals continues to be lacking. To bridge this gap, the National Institute of Health in Italy together with the National Office against Racial Discriminations, clinical centres, and TGD organizations carried out a cross-sectional study to define the sociodemographic profile, health-related behaviours, and experiences of healthcare access in Italian TGD adult population. METHODS: A national survey was conducted by Computer-Assisted Web Interviewing (CAWI) technique. Collected data were compared within the TGD subgroups and between TGD people and the Italian general population (IGP). RESULTS: TGD respondents were 959: 65% assigned female at birth (AFAB) and 35% assigned male at birth (AMAB). 91.8% and 8.2% were binary and non-binary TGD respondents, respectively. More than 20% of the TGD population reported to be unemployed with the highest rate detectable in AMAB and non-binary people. Cigarette smoking and binge drinking were higher in the TGD population compared with IGP (p < 0.05), affecting TGD subgroups differently. A significant lower percentage of AFAB TGD people reported having had screening for cervical and breast cancer in comparison with AFAB IGP (p < 0.0001, in both cases). Over 40% was the percentage of AFAB and non-binary TGD people accessing healthcare who felt discriminated against because of their gender identity. CONCLUSIONS: Our results are a first step towards a better understanding of the health needs of TGD people in Italy in order to plan the best policy choices for a more inclusive public health.

Controlling the configuration space topology of mechanical structures.

Linkages are mechanical devices constructed from rigid bars and freely rotating joints studied both for their utility in engineering and as mathematical idealizations in a number of physical systems. Recently, there has been a resurgence of interest in designing linkages in the physics community due to the concurrent developments of mechanical metamaterials, topological mechanics, and the discovery of anomalous rigidity in fiber networks and vertex models. These developments raise a natural question: to what extent can the motion of a linkage or mechanical structure be designed? Here, we describe a method to design the topology of the configuration space of a linkage by first identifying the manifold of critical points, then perturbing around such critical configurations. Unlike other methods, our methods are tractable and provide a simple visual toolkit for mechanism design. We demonstrate our procedure by designing a mechanism to gate the propagation of a soliton in a Kane-Lubensky chain of interconnected rotors.

Topological transitions in the configuration space of non-Euclidean origami.

Origami structures have been proposed as a means of creating three-dimensional structures from the micro- to the macroscale and as a means of fabricating mechanical metamaterials. The design of such structures requires a deep understanding of the kinematics of origami fold patterns. Here we study the configurations of non-Euclidean origami, folding structures with Gaussian curvature concentrated on the vertices, for arbitrary origami fold patterns. The kinematics of such structures depends crucially on the sign of the Gaussian curvature. As an application of our general results, we show that the configuration space of nonintersecting, oriented vertices with positive Gaussian curvature decomposes into disconnected subspaces; there is no pathway between them without tearing the origami. In contrast, the configuration space of negative Gaussian curvature vertices remains connected. This provides a new, and only partially explored, mechanism by which the mechanics and folding of an origami structure could be controlled.

Dietary habits affect fatty acid composition of visceral adipose tissue in subjects with colorectal cancer or obesity.

PURPOSE: Aim of this study was to identify a possible relationship among dietary fatty acids (FA) intake, FA adipose tissue (AT) profile and cancer condition in lean vs obese subjects affected or not by colorectal cancer (CRC). Actually, inadequate dietary habits together with physical inactivity are primary determinants of obesity and cancer risk. Changes in lipid metabolism play a crucial role in different types of cancer and key enzymes involved in lipid-metabolic pathways, such as stearoyl-coA-desaturase 1 (SCD-1), are differentially expressed in normal and cancer tissues. METHODS: Food frequency questionnaires (FFQ) were analyzed by Winfood software. FA were assessed by gas-liquid chromatography in visceral AT samples. Estimated desaturase activities were calculated as precursor FA/product FA ratio. Desaturase gene expressions were evaluated by RT-qPCR. RESULTS: Lean and obese CRC subjects showed inadequate dietary habits. In particular, lean CRC subjects showed increase in the intake of saturated FA, specifically palmitic (p = 0.0042) and stearic acid (p = 0.0091), and a corresponding reduction of monounsaturated FA consumption, in particular oleic acid (p = 0.002) with respect to lean without CRC. Estimated SCD-1 activity in AT was increased in all the groups vs lean without CRC (pANOVA = 0.029). CONCLUSIONS: Unhealthy eating habits, characterizing obese and CRC subjects, may influence the visceral AT profile and contribute to the alteration of the metabolic pathways. The quality of the diet, other than the quantity, can have a main role in the establishment of inflammatory microenvironment and in metabolic changes favouring CRC.

Consumption of extra-virgin olive oil rich in phenolic compounds improves metabolic control in patients with type 2 diabetes mellitus: a possible involvement of reduced levels of circulating visfatin.

AIM: Phenolic compounds naturally contained in extra-virgin olive oil (EVOO) have demonstrated anti-inflammatory and antioxidant properties. The present study aimed at evaluating the effects of a polyphenol-rich extra-virgin olive oil (EVOO) (high-polyphenol EVOO, HP-EVOO) on the metabolic control and the production of specific pro-/anti-inflammatory adipokines in overweight patients with type 2 diabetes mellitus (T2D). METHODS: Eleven overweight T2D patients not in treatment with insulin were invited to follow their habitual diet for a total of 8 weeks. During the first 4 weeks (wash-out period), they were asked to consume refined olive oil (ROO, polyphenols not detectable) and then to replace ROO with HP-EVOO (25 mL/day, 577 mg of phenolic compounds/kg) for the remaining 4 weeks. Anthropometric parameters, fasting glycaemia, glycated haemoglobin (HbA1c), high-sensitive C-reactive protein, plasma lipid profile, liver function and serum levels of TNF-α, IL-6, adiponectin, visfatin and apelin were assessed at the end of each 4-week period. RESULTS: HP-EVOO consumption significantly reduced fasting plasma glucose (P = 0.023) and HbA1c (P = 0.039) levels as well as BMI (P = 0.012) and body weight (P = 0.012). HP-EVOO ingestion determined a reduction in serum level of aspartate aminotransferase (AST, P = 0.0056) and alanine aminotransferase (ALT, P = 0.024). Serum visfatin levels strongly decreased after HP-EVOO ingestion (P = 0.0021). CONCLUSIONS: Daily consumption of polyphenol-rich EVOO might improve metabolic control and circulating inflammatory adipokines profile in overweight T2D patients.

Topological Mechanics of Origami and Kirigami.

Origami and kirigami have emerged as potential tools for the design of mechanical metamaterials whose properties such as curvature, Poisson ratio, and existence of metastable states can be tuned using purely geometric criteria. A major obstacle to exploiting this property is the scarcity of tools to identify and program the flexibility of fold patterns. We exploit a recent connection between spring networks and quantum topological states to design origami with localized folding motions at boundaries and study them both experimentally and theoretically. These folding motions exist due to an underlying topological invariant rather than a local imbalance between constraints and degrees of freedom. We give a simple example of a quasi-1D folding pattern that realizes such topological states. We also demonstrate how to generalize these topological design principles to two dimensions. A striking consequence is that a domain wall between two topologically distinct, mechanically rigid structures is deformable even when constraints locally match the degrees of freedom.

Spread of a carbapenem- and colistin-resistant Acinetobacter baumannii ST2 clonal strain causing outbreaks in two Sicilian hospitals.

BACKGROUND: Infections caused by multidrug-resistant (MDR) Acinetobacter baumannii have become an important healthcare-associated problem, particularly in intensive care units (ICUs). AIM: To investigate the emergence of carbapenem- and colistin-resistant A. baumannii infections in two Sicilian hospitals. METHODS: From October 2008 to May 2011, a period which included two Italian Nosocomial Infections Surveillance in ICUs network (SPIN-UTI) project surveys, all carbapenem-resistant A. baumannii isolates from the ICUs of two hospitals in Catania, Italy, were prospectively collected. Minimum inhibitory concentrations (MICs) were measured by agar dilution, and phenotypic testing for metallo-ß-lactamase (MBL) production was performed. Carbapenem resistance genes and their genetic elements were identified by polymerase chain reaction and sequencing. Genotypic relatedness was assessed by pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing. Patient-based surveillance was conducted using the SPIN-UTI protocol and previous antibiotic consumption was recorded. FINDINGS: Twenty-six carbapenem-resistant A. baumannii were identified. Imipenem and meropenem MICs ranged from 4 to >32 mg/L, and 15 isolates exhibited high-level colistin resistance (MICs >32 mg/L). PFGE demonstrated that all isolates belonged to a unique clonal type and were assigned to ST2 of the international clone II. They harboured an intrinsic blaOxA-51-like carbapenemase gene, blaOxA-82, which was flanked upstream by ISAba1. CONCLUSIONS: The dissemination of clonally related isolates of carbapenem-resistant A. baumannii in two hospitals is described. Simultaneous resistance to colistin in more than half of the isolates is a problem for effective antibiotic treatment. Prior carbapenem and colistin consumption may have acted as triggering factors.

Slack dynamics on an unfurling string.

An arch will grow on a rapidly deployed thin string in contact with a rigid plane. We present a qualitative model for the growing structure involving the amplification, rectification, and advection of slack in the presence of a steady stress field, validate our assumptions with numerical experiments, and pose new questions about the spatially developing motions of thin objects.

Protocatechuic acid and human disease prevention: biological activities and molecular mechanisms.

Epidemiological evidence has shown that a high dietary intake of vegetables and fruit rich in polyphenols is associated with a reduction of cancer incidence and mortality from coronary heart disease. The healthy effects associated with polyphenol consumption have made the study of the mechanisms of action a matter of great importance. In particular, the hydroxybenzoic acid protocatechuic acid (PCA) has been eliciting a growing interest for several reasons. Firstly, PCA is one of the main metabolites of complex polyphenols such as anthocyanins and procyanidins that are normally found at high concentrations in vegetables and fruit, and are absorbed by animals and humans. Since the daily intake of anthocyanins has been estimated to be much higher than that of other polyphenols, the nutritional value of PCA is increasingly recognized. Secondly, a growing body of evidence supports the concept that PCA can exert a variety of biological effects by acting on different molecular targets. It has been shown that PCA possesses antioxidant, anti-inflammatory as well as antihyperglycemic and neuroprotective activities. Furthermore, PCA seems to have chemopreventive potential because it inhibits the in vitro chemical carcinogenesis and exerts pro-apoptotic and anti-proliferative effects in different tissues. This review is aimed at providing an up-dated and comprehensive report on PCA giving a special emphasis on its biological activities and the molecular mechanisms of action most likely responsible for a beneficial role in human disease prevention.

Programmed buckling by controlled lateral swelling in a thin elastic sheet.

Recent experiments have imposed controlled swelling patterns on thin polymer films, which subsequently buckle into three-dimensional shapes. We develop a solution to the design problem suggested by such systems, namely, if and how one can generate particular three-dimensional shapes from thin elastic sheets by mere imposition of a two-dimensional pattern of locally isotropic growth. Not every shape is possible. Several types of obstruction can arise, some of which depend on the sheet thickness. We provide some examples using the axisymmetric form of the problem, which is analytically tractable.

Outbreak of KPC-3-producing, and colistin-resistant, Klebsiella pneumoniae infections in two Sicilian hospitals.

We report the first outbreak caused by colistin-resistant Klebsiella pneumoniae producing KPC-3 carbapenamase in two Italian hospitals. This spread occurred in 1 month, and was caused by eight colistin-resistant and carbapenem-resistant Klebsiella pneumoniae isolates from eight patients. A further three isolates were obtained from the intestinal tract and pharyngeal colonization. All isolates were multidrug-resistant (MDR), including being resistant to colistin, but they were susceptible to gentamicin and tigecycline. PCR detection showed that all isolates harboured the bla(KPC-3) gene associated with bla(SHV-11) , bla(TEM-1) and bla(OXA-9) . All K. pneumoniae isolates, genotyped by pulsed-field gel electrophoresis and multilocus sequence typing, belonged to the same sequence type (ST)258 clone. From our data and a review of the international literature, K. pneumoniae ST258 seems to be the most widespread genetic background for KPC dissemination in Europe.

Fasting and post-prandial adipose tissue lipoprotein lipase and hormone-sensitive lipase in obesity and type 2 diabetes.

BACKGROUND: Fasting and post-prandial abnormalities of adipose tissue (AT) lipoprotein lipase (LPL) and hormone- sensitive lipase (HSL) activities may have pathophysiological relevance in insulin-resistant conditions. AIM: The aim of this study was to evaluate activity and gene expression of AT LPL and HSL at fasting and 6 h after meal in two insulin-resistant groups - obese with Type 2 diabetes and obese without diabetes - and in non-diabetic normal-weight controls. MATERIAL/SUBJECTS AND METHODS: Nine obese subjects with diabetes, 10 with obesity alone, and 9 controls underwent measurements of plasma levels of glucose, insulin, and triglycerides before and after a standard fat-rich meal. Fasting and post-prandial (6 h) LPL and HSL activities and gene expressions were determined in abdominal subcutaneous AT needle biopsies. RESULTS: The diabetic obese subjects had significantly lower fasting and post-prandial AT heparin-releasable LPL activity than only obese and control subjects (p<0.05) as well as lower mRNA LPL levels. HSL activity was significantly reduced in the 2 groups of obese subjects compared to controls in both fasting condition and 6 h after the meal (p<0.05), while HSL mRNA levels were not different. There were no significant changes between fasting and 6 h after meal measurements in either LPL or HSL activities and gene expressions. CONCLUSIONS: Lipolytic activities in AT are differently altered in obesity and Type 2 diabetes being HSL alteration associated with both insulin-resistant conditions and LPL with diabetes per se. These abnormalities are similarly observed in the fasting condition and after a fat-rich meal.

Angiotensin blockade and matrix synthesis by glomerular epithelial cells in high glucose: a further experimental insight into the pathophysiology of diabetic nephropathy.

AIMS: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor-1 (AT-1) antagonists are used in the treatment of proteinuria of diabetic nephropathy. One of the major pathogenic events in this condition is represented by the alteration of the extracellular matrix protein synthesis by glomerular epithelial cells. MATERIALS AND METHODS: We evaluated the effects of the angiotensin converting enzyme inhibitor, Enalaprilat, and the AT-1 receptor antagonist, Losartan, on mRNA fibronectin and laminin synthesis by glomerular epithelial cells, in conditions mimicking hyperglycemia. RESULTS: In high glucose conditions, Enalaprilat reduced significantly the mRNA expression of fibronectin (p 0.03), but not significantly that of laminin. Losartan addition to high glucose incubated cells reduced (-30%) mRNA expression of fibronectin, and significantly (p 0.05) the mRNA expression of laminin. CONCLUSIONS: In addition to the known hemodynamic effects, the improvement of renal function in diabetic patients treated with these compounds may also be due to a modulator effect on extracellular matrix content and composition.

Undulated cylinders of charged diblock copolymers.

We study the cylinder to sphere morphological transition of diblock copolymers in aqueous solution with a hydrophobic block and a charged block. We find a metastable undulated cylinder configuration for a range of charge and salt concentrations which, nevertheless, occurs above the threshold where spheres are thermodynamically favorable. By modeling the shape of the cylinder ends, we find that the free-energy barrier for the transition from cylinders to spheres is quite large and that this barrier falls significantly in the limit of high polymer charge and low solution salinity. This suggests that observed undulated cylinder phases are kinetically trapped structures.

The acquisition of an insulin-secreting phenotype by HGF-treated rat pancreatic ductal cells (ARIP) is associated with the development of susceptibility to cytokine-induced apoptosis.

The elucidation of mechanisms regulating the regeneration and survival of pancreatic beta cells has fundamental implications in the cell therapy of type 1 diabetes. The present study had the following three aims: 1. to investigate whether pancreatic ductal epithelial cells can be induced to differentiate into insulin-producing cells by exposing them to hepatocyte growth factor (HGF); 2. to characterize some of the molecular events leading to their differentiation toward a beta-cell-like phenotype; 3. to evaluate the susceptibility of newly differentiated insulin-secreting cells to cytokine-induced apoptosis, a mechanism of beta-cell destruction occurring in type 1 diabetes. We demonstrated that HGF-treated rat pancreatic ductal cell line (ARIP) cells acquired the capability to transcribe the insulin gene and translate its counterpart protein. HGF-treated cells also exhibited a glucose-dependent capability to secrete insulin into the cultured medium. Expression analysis of some of the genes regulating pancreatic beta-cell differentiation revealed a time-dependent transcription of neurogenin-3 and Neuro-D in response to HGF. Finally, we determined the susceptibility to proinflammatory cytokine (PTh1)-induced apoptosis by incubating HGF-treated and untreated ARIP cells with a cocktail of interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). Such treatment induced apoptotic death, as determined by the TUNEL technique, in about 40% of HGF-treated, insulin-secreting ARIP cells, while untreated ARIP cells were resistant to PTh1-induced apoptosis. In conclusion, we showed that HGF promotes the differentiation of ARIP cells into pancreatic beta-cell-like cells, and that the differentiation toward an insulin-secreting phenotype is associated with the appearance of susceptibility to cytokine-induced apoptosis.

Effects of counterion fluctuations in a polyelectrolyte brush.

We investigate the effect of counterion fluctuations in a single polyelectrolyte brush in the absence of added salt by systematically expanding the counterion free energy about Poisson-Boltzmann mean-field theory. We find that for strongly charged brushes, there is a collapse regime in which the brush height decreases with increasing charge on the polyelectrolyte chains. The transition to this collapsed regime is similar to the liquid-gas transition, which has a first-order line terminating at a critical point. We find that, for monovalent counterions, the transition is discontinuous in theta solvent, while for multivalent counterions, the transition is generally continuous. For collapsed brushes, the brush height is not independent of grafting density as it is for osmotic brushes, but scales linear with it.

Angiotensin-converting enzyme inhibition modulates high-glucose-induced extracellular matrix changes in mouse glomerular epithelial cells.

BACKGROUND/AIM: Extracellular matrix alterations are involved in the pathogenesis of diabetic nephropathy. We evaluated the effects of high glucose concentrations and inhibition of angiotensin-converting enzyme on the laminin and fibronectin production by glomerular epithelial cells. METHODS: Glomerular epithelial cells were cultured in 5 and 30 mmol/l glucose, with and without enalaprilat (0.3 mmol/l). Laminin and fibronectin were measured (35S-methionine, immunoprecipitation), and their mRNA expression was evaluated (RT-PCR). RESULTS: The laminin concentration was higher in the cells than in the medium, where an increase of its content was observed under high-glucose conditions (p < 0.01). Fibronectin, found only in the medium, was not modified by the high glucose concentration. Following enalaprilat administration, the laminin concentration was decreased under high-glucose conditions, both in the cell and in the medium (p < 0.001), whereas the fibronectin concentration was increased under high-glucose conditions (p < 0.001). The mRNA expression of laminin and fibronectin under high-glucose conditions only slightly increased. Enalaprilat decreased the fibronectin mRNA synthesis dramatically (>50%, p < 0.0001) under high-glucose conditions. CONCLUSIONS: Enalaprilat normalizes the abnormal, high-glucose-induced concentration of laminin, while it decreases the fibronectin synthesis. The improvement of the renal function in diabetic patients treated with angiotensin-converting enzyme inhibitors may, in part, be due to a modulator effect on extracellular matrix content and composition.

Bogomol'nyi, Prasad, and Sommerfield configurations in smectics.

It is typical in smectic liquid crystals to describe elastic deformations with a linear theory when the elastic strain is small. In smectics, certain essential nonlinearities arise from the requirement of rotational invariance. By employing the Bogomol'nyi, Prasad, and Sommerfield decomposition and relying on boundary conditions and geometric invariants, we have found a large class of exact solutions. We introduce an approximation for the deformation profile far from a spherical inclusion and find an enhanced attractive interaction at long distances due to the nonlinear elasticity, confirmed by numerical minimization.

Hormonal regulation of cytokine release by human fetal membranes at term gestation: effects of oxytocin, hydrocortisone and progesterone on tumour necrosis factor-alpha and transforming growth factor-beta 1 output.

Inflammatory cytokines can play an important role in the biomolecular processes leading to labour by regulating prostaglandin production in intrauterine tissues. In the setting of intrauterine infection, an increased production of these cytokines by placenta, decidua and fetal membranes occurs and is responsible for the onset and maintenance of preterm labour. However, the factors involved in the control of cytokine release by these tissues in normal pregnancy at term are still largely unknown. We investigated the possibility that the synthesis and release of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) by human fetal membranes at term gestation is regulated by several hormones potentially involved either in the maintenance of pregnancy or in the parturitional process. In the present study, the effects of hydrocortisone, progesterone and oxytocin on TNF-alpha and TGF-beta1 release by explants of fetal membranes at term gestation were evaluated. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the effect of the above hormones on mRNA expression; TNF-alpha and TGF-beta1 release in culture medium was quantitifed by ELISA assays. Results show that both tissue mRNA expression for TNF-alpha and TNF-alpha release in culture medium were significantly increased by oxytocin, but not by hydrocortisone and progesterone. On the contrary, all the hormones tested increased both tissue TGF-beta1 mRNA expression and release in culture medium. These findings suggest that TNF-alpha and TGF-beta1 production by human fetal membranes in uncomplicated pregnancy at term is selectively modulated by oxytocin, hydrocortisone and progesterone.