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The placenta is crucial to fetal development and performs vital functions such as nutrient exchange, waste removal and hormone regulation. Abnormal placental development can lead to conditions such as fetal growth restriction, pre-eclampsia and stillbirth, affecting both immediate and long-term fetal health. Placental development is a highly complex process involving interactions between maternal and fetal components, imprinted genes, signaling pathways, mitochondria, fetal sexomes and environmental factors such as diet, supplementation and exercise. Probiotics have been shown to make a significant contribution to prenatal health, placental health and fetal development, with associations with reduced risk of preterm birth and pre-eclampsia, as well as improvements in maternal health through effects on gut microbiota, lipid metabolism, vaginal infections, gestational diabetes, allergic diseases and inflammation. This review summarizes key studies on the influence of dietary supplementation on placental development, with a focus on the role of probiotics in prenatal health and fetal development.

Nitric oxide (NO) is a highly versatile gasotransmitter that has first been shown to regulate cardiovascular function and then to exert tight control over a much broader range of processes, including neurotransmitter release, neuronal excitability, and synaptic plasticity. Endothelial NO synthase (eNOS) is usually far from the mind of synaptic neurophysiologists, who have focused most of their attention on neuronal NO synthase (nNOS) as the primary source of NO at the neurovascular unit (NVU). Nevertheless, the available evidence suggests that eNOS could also contribute to generating the burst of NO that, serving as volume intercellular messenger, is produced in response to neuronal activity in the brain parenchyma. Herein, we review the role of eNOS in both the regulation of cerebral blood flow and of synaptic plasticity and discuss the mechanisms by which cerebrovascular endothelial cells may transduce synaptic inputs into a NO signal. We further suggest that eNOS could play a critical role in vascular-to-neuronal communication by integrating signals converging onto cerebrovascular endothelial cells from both the streaming blood and active neurons.

(1) Background: Acute kidney injury (AKI) kidneys have high non-utilization rates due to concerns regarding unfavorable outcomes. In this paper, we aimed to review the past, present, and future opinions on AKI kidneys. (2) Methods: A PubMed search was conducted for topics relevant to AKI kidney transplantation. (3) Results: Current short- and long-term data on AKI kidneys have demonstrated good outcomes including favorable graft function and survival. The role of procurement biopsies is controversial, but they have been shown to be beneficial in AKI kidneys by allowing clinicians to differentiate between reversible tubular injury and irreversible cortical necrosis. Machine perfusion has also been applied to AKI kidneys and has been shown to reduce delayed graft function (DGF). The incidence of DGF increases with AKI severity and its management can be challenging. Strategies employed to counteract this have included early initiation of dialysis after kidney transplantation, early targeting of adequate immunosuppression levels to minimize rejection risk, and establishment of outpatient dialysis. (4) Conclusions: Despite good outcomes, there continue to be barriers that impact AKI kidney utilization. Successful strategies have included use of procurement biopsies or machine perfusion and expectant management of DGF. With increasing experience, better use of AKI kidneys can result in additional opportunities to expand the donor pool.

Films and fibers of syndiotactic polystyrene (sPS), being amorphous or exhibiting nanoporous crystalline (NC) or dense crystalline phases, were loaded with salicylic acid (SA), a relevant non-volatile antimicrobial molecule. In the first section of the paper, sPS/SA co-crystalline (CC) δ form is characterized, mainly by wide angle X-ray diffraction (WAXD) patterns and polarized Fourier transform infrared (FTIR) spectra. The formation of sPS/SA δ CC phases allows the preparation of sPS fibers even with a high content of the antibacterial guest, which is also retained after repeated washing procedures at 65 °C. A preparation procedure starting from amorphous fibers is particularly appropriate because involves a direct formation of the CC δ form and a simultaneous axial orientation. The possibility of tuning drug amount and release kinetics, by simply selecting suitable crystalline phases of a commercially available polymer, makes sPS fibers possibly useful for many applications. In particular, fibers with δ CC forms, which retain SA molecules in their crystalline phases, could be useful for antimicrobial textiles and fabrics. Fibers with the dense γ form which easily release SA molecules, because they are only included in their amorphous phases, could be used for promising SA-based preparations for antibacterial purposes in food processing and preservation and public health. Finally, using a cell-based assay system and antibacterial tests, we investigated the cellular activity, toxicity and antimicrobial properties of amorphous, δ CC forms and dense γ form of sPS fibers loaded with different contents of SA.

Store-operated Ca 2+ entry (SOCE) is activated in response to the inositol-1,4,5-trisphosphate (InsP 3 )-dependent depletion of the endoplasmic reticulum (ER) Ca 2+ store and represents a ubiquitous mode of Ca 2+ influx. In vascular endothelial cells, SOCE regulates a plethora of functions that maintain cardiovascular homeostasis, such as angiogenesis, vascular tone, vascular permeability, platelet aggregation, and monocyte adhesion. The molecular mechanisms responsible for SOCE activation in vascular endothelial cells have engendered a long-lasting controversy. Traditionally, it has been assumed that the endothelial SOCE is mediated by two distinct ion channel signalplexes, i.e., STIM1/Orai1 and STIM1/Transient Receptor Potential Canonical 1(TRPC1)/TRPC4. However, recent evidence has shown that Orai1 can assemble with TRPC1 and TRPC4 to form a non-selective cation channel with intermediate electrophysiological features. Herein, we aim at bringing order to the distinct mechanisms that mediate endothelial SOCE in the vascular tree from multiple species (e.g., human, mouse, rat, and bovine). We propose that three distinct currents can mediate SOCE in vascular endothelial cells: (1) the Ca 2+ -selective Ca 2+ -release activated Ca 2+ current (I CRAC ), which is mediated by STIM1 and Orai1; (2) the store-operated non-selective current (I SOC ), which is mediated by STIM1, TRPC1, and TRPC4; and (3) the moderately Ca 2+ -selective, I CRAC -like current, which is mediated by STIM1, TRPC1, TRPC4, and Orai1.

Background: A validity and reliability assessment of inertial measurement unit (IMU)-derived joint angular kinematics during walking is a necessary step for motion analysis in the lower extremity prosthesis user population. This study aimed to assess the accuracy and reliability of an inertial measurement unit (IMU) system compared to an optical motion capture (OMC) system in transtibial prosthesis (TTP) users., Methods: Thirty TTP users were recruited and underwent simultaneous motion capture from IMU and OMC systems during walking. Reliability and validity were assessed using intra- and inter-subject variability with standard deviation (S.D.), average S.D., and intraclass correlation coefficient (ICC)., Results: The intra-subject S.D. for all rotations of the lower limb joints were less than 1° for both systems. The IMU system had a lower mean S.D. ( o ), as seen in inter-subject variability. The ICC revealed good to excellent agreement between the two systems for all sagittal kinematic parameters., Conclusion: All joint angular kinematic comparisons supported the IMU system's results as comparable to OMC. The IMU was capable of precise sagittal plane motion data and demonstrated validity and reliability to OMC. These findings evidence that when compared to OMC, an IMU system may serve well in evaluating the gait of lower limb prosthesis users.

Frailty is a clinical condition closely related to aging which is characterized by a multidimensional decline in biological reserves, a failure of physiological mechanisms and vulnerability to minor stressors. Chronic inflammation, the impairment of endothelial function, age-related endocrine system modifications and immunosenescence are important mechanisms in the pathophysiology of frailty. Endothelial progenitor cells (EPCs) are considered important contributors of the endothelium homeostasis and turn-over. In the elderly, EPCs are impaired in terms of function, number and survival. In addition, the modification of EPCs' level and function has been widely demonstrated in atherosclerosis, hypertension and diabetes mellitus, which are the most common age-related diseases. The purpose of this review is to illustrate the role of EPCs in frailty. Initially, we describe the endothelial dysfunction in frailty, the response of EPCs to the endothelial dysfunction associated with frailty and, finally, interventions which may restore the EPCs expression and function in frail people.

During pregnancy, SARS-CoV-2 infection is associated with several adverse outcomes, including an increased risk of pre-eclampsia, preterm delivery, hypertensive disorders, gestational diabetes, and fetal growth restriction related to the development of placenta vascular abnormalities. We analyzed human placenta from full-term, uncomplicated pregnancies with SARS-CoV-2 infection during the first, second, or third trimesters of gestation. We studied, by the immunohistochemistry technique, the expression of CD34 and podoplanin (PDPN) as markers of vasculogenesis to find any differences. As secondary outcomes, we correlated maternal symptoms with placental histological alterations, including fibrin deposits, lymphocyte infiltration in the villi, edema, and thrombi. Our results showed a PDPN expression around the villous stroma as a plexiform network around the villous nucleus of fetal vessels; significant down-regulation was observed in the villous stroma of women infected during the third trimester. CD34 showed no changes in expression levels. During SARS-CoV-2 infection, the most common maternal symptoms were fever, anosmia, ageusia and asthenia, and the majority were treated with paracetamol, corticosteroids and azithromycin. Patients that required multiple symptomatic treatments evidenced a large amount of fibrin deposition in the villi. Certainly, PDPN plays a key role in healthy placental vasculogenesis and thus in its proper physiology, and SARS-CoV-2 surely alters its normal expression. Further studies are necessary to understand what mechanisms are being altered to try to avoid possible complications for both the mother and fetus in terms of the contagions that will still occur.

Benzoic acid (BA) and its derivatives are very attractive because of their pharmacological properties, such as antioxidant, radical-regulating, antiviral, antitumor, anti-inflammatory, antimicrobial and antifungal. Syndiotactic polystyrene (sPS) and poly(2,6-dimethyl-1,4-phenylene)oxide (PPO) films exhibiting co-crystalline phases with BA were prepared and characterized by WAXD, FTIR and polarized FTIR measurements. The FTIR measurements clearly showed that BA was present mainly as a dimer in the crystalline channels of the ε form of sPS as well as in the α form of PPO, as generally occurs not only in the solid state but also in organic dilute solutions. BA was instead present as isolated molecules in the crystalline cavities of the δ form of sPS. In fact, the FTIR spectra of BA guest molecules exhibited vibrational peaks close to those of BA in its vapor phase. Hence, the nanoporous-crystalline δ form of sPS not only avoids additive aggregation but also leads to the separation of dimeric molecules and the segregation of monomeric BA.

The development of a Lewis acid-catalyzed, intramolecular ring-opening benzannulation of 5-(indolyl)2,3-dihydrofuran acetals is described. The resulting 1-hydroxycarbazole-2-carboxylates are formed in up to 90% yield in 1 h. The dihydrofuran acetals are readily accessed from the reactions of enol ethers and α-diazo-β-indolyl-β-ketoesters. To highlight the method's synthetic utility, a formal total synthesis of murrayafoline A, a bioactive carbazole-containing natural product, was undertaken.

Tumor diseases are unfortunately quick spreading, even though numerous studies are under way to improve early diagnosis and targeted treatments that take into account both the different characteristics associated with the various tumor types and the conditions of individual patients. In recent years, studies have focused on the role of ion channels in tumor development, as these proteins are involved in several cellular processes relevant to neoplastic transformation. Among all ion channels, many studies have focused on the superfamily of Transient Receptor Potential (TRP) channels, which are non-selective cation channels mediating extracellular Ca 2+ influx. In this review, we examined the role of different endothelial TRP channel isoforms in tumor vessel formation, a process that is essential in tumor growth and metastasis.

Outcomes of users provided with a commercial ESR Vari-Flex foot (Össur, Reykjavik, Iceland) and a locally designed sPace foot were investigated. Step activity with users' own prosthetic foot compared to the sPace foot was explored., Methods: Eleven individuals with unilateral trans-tibial amputation participated and were provided with an sPace and Vari-Flex foot. Ten- and twenty-meter walk tests (10/20MWT) at comfortable and fast walking speeds (CWS/FWS), the two-minute walk test (2-MWT) and Comprehensive High-Level Activity Mobility Predictor (CHAMP) were administered. A subgroup was provided a pedometer to record their steps over a 7-day period in their own foot and later the sPace., Results: The sPace foot performed well in a battery of high-level mobility outcome measures. On CHAMP, participants scored 16.94 ± 5.41 and 16.72 ± 6.09 with the sPace and Vari-Flex feet, respectively. Subgroup testing of step activity showed 4490 ± 3444 steps in users' own feet and 3115 ± 1967 in the sPace foot, p = 0.176., Conclusions: Participants using the sPace foot were capable of performing walking, high-level mobility and activity outcome measures.

(1) Background: A sustainable casting system that combines the use of a polystyrene bag, a prosthetic liner and a vacuum system was developed to reduce fabrication time while maintaining comfort for the trans-tibial prosthesis user. (2) Methods: Eight prosthetists (28.7 ± 8.25 years old) fit ten trans-tibial prosthesis wearers (46 ± 12.4 years old) with two types of total surface bearing (TSB) prostheses; a polystyrene bead (PS) prosthesis and a plaster of paris (POP) prosthesis. Duration of casting and combined mean peak pressure was measured at six locations on the residual limb using Force Sensing Resistors (FSR). A pressure uniformity score (%) was determined. Socket Comfort Scale (SCS) was also measured. (3) Results: Duration of casting for the POP method was 64.8 ± 9.53 min and 7.8 ± 2 min for the PS method, ( p = 0.006). Pressure uniformity in the POP prosthesis was 79.3 ± 6.54 and 81.7 ± 5.83 in the PS prosthesis ( p = 0.027). SCS in both prosthesis types were equivalent. (4) Conclusion: A rapid fit PS prosthesis was developed, with significantly shorter duration than the traditional POP method. Socket pressure uniformity was confirmed and improved in the PS method. Socket comfort was equal between the two prothesis types.

Gene expression is controlled by epigenetic deregulation, a hallmark of cancer. The DNA methylome of canine diffuse large B-cell lymphoma (cDLBCL), the most frequent malignancy of B-lymphocytes in dog, has recently been investigated, suggesting that aberrant hypermethylation of CpG loci is associated with gene silencing. Here, we used a multi-omics approach (DNA methylome, transcriptome and copy number variations) combined with functional in vitro assays, to identify putative tumour suppressor genes subjected to DNA methylation in cDLBCL. Using four cDLBCL primary cell cultures and CLBL-1 cells, we found that CiDEA , MAL and PCDH17 , which were significantly suppressed in DLBCL samples, were hypermethylated and also responsive (at the DNA, mRNA and protein level) to pharmacological unmasking with hypomethylating drugs and histone deacetylase inhibitors. The regulatory mechanism underneath the methylation-dependent inhibition of those target genes expression was then investigated through luciferase and in vitro methylation assays. In the most responsive CpG-rich regions, an in silico analysis allowed the prediction of putative transcription factor binding sites influenced by DNA methylation. Interestingly, regulatory elements for AP2, MZF1, NF-kB, PAX5 and SP1 were commonly identified in all three genes. This study provides a foundation for characterisation and experimental validation of novel epigenetically-dysregulated pathways in cDLBCL.

Non-invasive prenatal testing (NIPT) is based on the detection and characterization of circulating cell-free fetal DNA (ccffDNA) in maternal plasma and aims to identify genetic abnormalities. At present, commercial NIPT kits can detect only aneuploidies, small deletions and insertions and some paternally inherited single-gene point mutations causing genetic diseases, but not maternally inherited ones. In this work, we have developed two NIPT assays, based on the innovative and sensitive droplet digital PCR (ddPCR) technology, to identify the two most common β thalassemia mutations in the Mediterranean area (β + IVSI-110 and β 0 39), maternally and/or paternally inherited, by fetal genotyping. The assays were optimized in terms of amplification efficiency and hybridization specificity, using mixtures of two genomic DNAs with different genotypes and percentages to simulate fetal and maternal circulating cell-free DNA (ccfDNA) at various gestational weeks. The two ddPCR assays were then applied to determine the fetal genotype from 52 maternal plasma samples at different gestational ages. The diagnostic outcomes were confirmed for all the samples by DNA sequencing. In the case of mutations inherited from the mother or from both parents, a precise dosage of normal and mutated alleles was required to determine the fetal genotype. In particular, we identified two diagnostic ranges for allelic ratio values statistically distinct and not overlapping, allowing correct fetal genotype determinations for almost all the analyzed samples. In conclusion, we have developed a simple and sensitive diagnostic tool, based on ddPCR, for the NIPT of β + IVSI-110 and β 0 39 mutations paternally and, for the first time, maternally inherited, a tool, which may be applied to other single point mutations causing monogenic diseases.

The military are selected on the basis of physical standards and are regularly involved in strong physical activities, also related to particular sports training. The aims of the study were to analyze the effect of a 7-month military training program on body composition variables and the suitability of specific 'bioelectrical impedance vector analysis' (spBIVA), compared to DXA, to detect the changes in body composition. A sample of 270 male Brazilian cadets (19.1 ± 1.1 years), composed of a group practicing military physical training routine only (MT = 155) and a group involved in a specific sport training (SMT = 115), were measured by body composition assessments (evaluated by means of DXA and spBIVA) at the beginning and the end of the military routine year. The effect of training on body composition was similar in SMT and MT groups, with an increase in LST. DXA and spBIVA were correlated, with specific resistance (Rsp) and reactance (Xcsp) positively related to fat mass (FM), FM%, LST, and lean soft tissue index (LSTI), and phase angle positively related to LST and LSTI. Body composition variations due to physical training were recognized by spBIVA: the increase in muscle mass was indicated by the phase angle and Xcsp increase, and the stability of FM% was consistent with the unchanged values of Rsp. Military training produced an increase in muscle mass, but no change in FM%, independently of the sample characteristics at baseline and the practice of additional sports. SpBIVA is a suitable technique for the assessment of body composition in military people.

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the swelling of multiple joints, pain and stiffness, and accelerated atherosclerosis. Sustained immune response and chronic inflammation, which characterize RA, may induce endothelial activation, damage and dysfunction. An equilibrium between endothelial damage and repair, together with the preservation of endothelial integrity, is of crucial importance for the homeostasis of endothelium. Endothelial Progenitor Cells (EPCs) represent a heterogenous cell population, characterized by the ability to differentiate into mature endothelial cells (ECs), which contribute to vascular homeostasis, neovascularization and endothelial repair. A modification of the number and function of EPCs has been described in numerous chronic inflammatory and auto-immune conditions; however, reports that focus on the number and functions of EPCs in RA are characterized by conflicting results, and discrepancies exist among different studies. In the present review, the authors describe EPCs' role and response to RA-related endothelial modification, with the aim of illustrating current evidence regarding the level of EPCs and their function in this disease, to summarize EPCs' role as a biomarker in cardiovascular comorbidities related to RA, and finally, to discuss the modulation of EPCs secondary to RA therapy.

For poly(2,6-dimethyl-1,4-phenylene)oxide (PPO) films exhibiting nanoporous-crystalline (NC) phases, c ⟂ orientation (i.e., crystalline polymer chain axes being preferentially perpendicular to the film plane) is obtained by crystallization of amorphous films, as induced by sorption of suitable low-molecular-mass guest molecules. The occurrence of c ⟂ orientation is relevant for applications of NC PPO films because it markedly increases film transparency as well as guest diffusivity. Surprisingly, we show that the known crystallization procedures lead to c = 42 ± 2 J/g).⟂ oriented thick (50-300 μm) films and to unoriented thin (≤20 μm) films. This absence of crystalline phase orientation for thin films is rationalized by fast guest sorption kinetics, which avoid co-crystallization in confined spaces and hence inhibit formation of flat-on lamellae. For thick films exhibiting c ⟂ orientation, sigmoid kinetics of guest sorption and of thickening of PPO films are observed, with inflection points associated with guest-induced film plasticization. Corresponding crystallization kinetics are linear with time and show that co-crystal growth is poorly affected by film plasticization. An additional relevant result of this study is the linear relationship between WAXD crystallinity index and DSC melting enthalpy, which allows evaluation of melting enthalpy of the NC α form of PPO (ΔH m ο = 42 ± 2 J/g).

Cancer cells shed a heterogenous mixture of extracellular vesicles (EVs), differing in both size and composition, which likely influence physiological processes in different manners. However, how cells differentially control the shedding of these EV populations is poorly understood. Here, we show that miR-1227, which is enriched in prostate cancer EVs, compared to the cell of origin, but not in EVs derived from prostate benign epithelial cells, induces the shedding of large EVs (such as large oncosomes), while inhibiting the shedding of small EVs (such as exosomes). RNA sequencing from cells stably expressing miR-1227, a modified RISCTRAP assay that stabilizes and purifies mRNA-miR-1227 complexes for RNA sequencing, and in silico target prediction tools were used to identify miR-1227 targets that may mediate this alteration in EV shedding. The COPII vesicle protein SEC23A emerged and was validated by qPCR, WBlot, and luciferase assays as a direct target of miR-1227. The inhibition of SEC23A was sufficient to induce the shedding of large EVs. These results identify a novel mechanism of EV shedding, by which the inhibition of SEC23A by miR-1227 induces a shift in EV shedding, favoring the shedding of large EV over small EV.

Background: The HUMAC Balance System (HBS) offers valid measurement of balance, and the arm crank exercise test (ACE) is a valid measure of physiological capacity. Neither have been used to evaluate associations between balance and physiological capacity in lower-limb amputees., Methods: Thirty-five participants with lower-limb amputations were recruited. Standing balance (center of pressure) was evaluated during eyes opened (EO) and eyes closed (EC) conditions using the HBS. Participants performed ACE graded exercise testing (GXT) to evaluate aerobic capacity. Spearman's rho was used to identify relationships between variables. Cut-points for three groups were generated for time on ACE. Mann-Whitney U tests were used to explore significant differences in variables of balance and ACE between low and high performers., Results: Relationships between variables of eyes open displacement (EOD), eyes open velocity (EOV), eyes closed displacement (ECD), and eyes closed velocity (ECV) were significant ( p < 0.05), and high performers with EO also performed best with EC. Longer exercise times were significantly associated with increased HR peak , VO 2peak , VE peak , and RER peak ( p < 0.05). HR peak (143.0 ± 30.6 b/min), VO 2peak (22.7 ± 7.9 and 10.6 ± 4.7 mL/kg/min), VE peak (80.2 ± 22.2 and 33.2 ± 12.7 L/min), and RER peak (1.26 ± 0.08 and 1.13 ± 0.11) were significantly greater in high performers than low performers, respectively ( p < 0.05). There was no significant association among VO 2peak and any balance task variables; however, there were significant associations between some balance and physiological variables., Conclusions: Findings differentiated high and low performers; however, participants were still well below able-bodied norms of physical capacity. Training to mitigate deconditioning is suggested.

Delta (δ) and epsilon (ε) co-crystalline forms of syndiotactic polystyrene with a carboxylic acid guest were obtained by sorption of liquid hexanoic acid in syndiotactic polystyrene films exhibiting delta and epsilon nanoporous-crystalline forms. The characterization study is facilitated by axially stretched syndiotactic polystyrene films, used both for polarized FTIR spectra and for WAXD fiber patterns. Particularly informative are two carbonyl-stretching FTIR peaks, attributed to monomeric and dimeric hexanoic acid. The dichroism of these carbonyl peaks indicates that both delta and epsilon phases are able to include hexanoic acid as isolated guest molecules, while only the epsilon phase is also able to include dimeric hexanoic acid molecules in its crystalline channels. The inclusion of both isolated and dimeric hexanoic acid species in the epsilon form crystalline channels produces extremely fast hexanoic acid uptakes by syndiotactic polystyrene epsilon form films.

Poly(ʟ-lactide) (PLLA) films, even of high thickness, exhibiting co-crystalline and crystalline α phases with their chain axes preferentially perpendicular to the film plane (c ⊥ orientation) have been obtained. This c ⊥ orientation, unprecedented for PLLA films, can be achieved by the crystallization of amorphous films as induced by low-temperature sorption of molecules being suitable as guests of PLLA co-crystalline forms, such as N , N -dimethylformamide, cyclopentanone or 1,3-dioxolane. This kind of orientation is shown and quantified by two-dimensional wide-angle X-ray diffraction (2D-WAXD) patterns, as taken with the X-ray beam parallel to the film plane (EDGE patterns), which present all the hk0 arcs centered on the meridian. PLLA α-form films, as obtained by low-temperature guest-induced crystallization, also exhibit high transparency, being not far from those of the starting amorphous films.

Recent events in prisons during the COVID-19 pandemic showed how the health situation and overcrowding in prisons are a source of high risk to the health and physical and mental well-being of the prison population and how this has become an important medical problem. The original purpose of this study, which was initially planned to last 6 months, was to examine the effects of a training program on cardio-respiratory capacity, resistance to dynamic strength of the upper and lower body and muscle mass. Following the COVID-19 pandemic, the purpose was subsequently modified by highlighting whether and which deficiencies occurred as a result of the absence of physical activity. Forty adult men between 35 and 55 years of age with more than 1 year of detention were selected and randomly divided into two groups: the experimental group and control group. The fitness training protocol of the experimental group consisted of three weekly sessions lasting 90 min, while control group subjects followed a walk of 30-60 min three days a week without running or resistance training. The unpaired and paired t-tests revealed significant effects of both health status and fitness level ( p < 0.05; p < 0.01) on group training. The results of this research show that prisoners can improve their fitness and health through participation in physical education programs. This conclusion is especially important for prisoners who have to serve very long prison sentences and who are at great risk of showing poor physical condition levels.

Step counts and oxygen consumption have yet to be reported during the 2-min walk test (2MWT) test in persons with lower-limb amputations (LLA). The purpose of this study was to determine step counts and oxygen consumption during the 2MWT in LLA. Thirty-five men and women walked for two minutes as quickly as possible while wearing activity monitors (ActiGraph Link on the wrist (LW) and ankle (LA), Garmin vivofit ® 3 on the wrist (VW) and ankle (VA), and a modus StepWatch on the ankle (SA), and a portable oxygen analyzer. The StepWatch on the ankle (SA) and the vivofit3 on the wrist (VW) had the least error and best accuracy of the activity monitors studied. While there were no significant differences in distance walked, oxygen consumption (VO 2 ) or heart rate (HR) between sexes or level of amputation ( p > 0.05), females took significantly more steps than males ( p = 0.034), and those with unilateral transfemoral amputations took significantly fewer steps than those with unilateral transtibial amputations ( p = 0.023). The VW and SA provided the most accurate step counts among the activity monitors and were not significantly different than hand counts. Oxygen consumption for all participants during the 2MWT was 8.9 ± 2.9 mL/kg/min, which is lower than moderate-intensity activity. While some may argue that steady-state activity has not yet been reached in the 2MWT, it may also be possible participants are not walking as fast as they can, thereby misclassifying their performance to a lower standard.

Two different zinc-based metal-organic frameworks (MOFs) were investigated to remove one of the most used fluoroquinolone antibiotic, Ofloxacin (OFL), from polluted water. The most common zeolitic imidazolate framework-8 (ZIF-8) and the green Zn(II) and benzene-1,3,5-tri-carboxylate (Zn 3 (BTC) 2 ) were prepared through a facile synthetic route and characterized by means of Fourier-Transform Infrared (FT-IR) Spectroscopy, X-ray Powder Diffraction (XRPD), and Scanning Electron Microscopy (SEM) analyses. The two MOFs were compared in terms of both adsorption and kinetic aspects under real conditions (tap water, natural pH). Results showed that OFL was adsorbed in remarkable amounts, 95 ± 10 and 25.3 ± 0.8 mg g -1 on ZIF-8 and Zn 3 (BTC) 2 , respectively, following different mechanisms. Specifically, a Langmuir model well described the ZIF-8 profile, while for Zn 3 (BTC) 2 , cooperative adsorption occurred. Moreover the kinetic results were quite different, pseudo-second-order and sigmoidal, respectively. The suitability of ZIF-8 and Zn 3 (BTC) 2 as adsorbent phases for water depollution was tested on tap water samples spiked with OFL 10 µg L -1 . The obtained removal efficiencies, of 88% for ZIF-8 and 72% for Zn 3 (BTC) 2 , make these materials promising candidates for removing fluoroquinolone antibiotics (FQs) from polluted waters, notwithstanding their limited reusability in tap water, as demonstrated by in-depth characterization of the two MOFs after usage.

High-porosity monolithic composite aerogels of syndiotactic polystyrene (sPS) and poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) containing reduced graphene oxide (r-GO) were prepared and characterized. The composite aerogels obtained by supercritical carbon dioxide (scCO 2 ) extraction of sPS/r-GO and PPO/r-GO gels were characterized by a fibrillar morphology, which ensured good handling properties. The polymer nanoporous crystalline phases obtained within the aerogels led to high surface areas with values up to 440 m 2 g -1 . The role of r-GO in aerogels was studied in terms of catalytic activity by exploring the oxidation capacity of composite PPO and sPS aerogels toward benzyl alcohol in diluted aqueous solutions. The results showed that, unlike sPS/r-GO aerogels, PPO/r-GO aerogels were capable of absorbing benzyl alcohol from the diluted solutions, and that oxidation of c.a. 50% of the sorbed benzyl alcohol molecules into benzoic acid occurred.

Films exhibiting co-crystalline (CC) phases between a polymer host and low-molecular-mass guest molecules are relevant for many applications. As is usual for semi-crystalline polymers, axially oriented films can give relevant information on the crystalline structure, both by Wide Angle X-ray diffraction fiber patterns and by polarized Fourier-transform infrared spectroscopy. Axially oriented CC phases of poly(2,6-dimethyl-1,4-phenylene)oxide (PPO) with 1,3,5-trimethylbenzene (mesitylene) can be simply obtained by the stretching of CC PPO films. In fact, due to the plasticization effect of this highly boiling guest, PPO orientation can occur in a stretching temperature range (170-175 °C) nearly 50 °C lower than that generally needed for PPO films (220-230 °C). This low stretching temperature range allows avoidance of polymer oxidation, as well as formation of the mesomorphic dense γ PPO phase. Axially oriented CC phases of PPO with toluene, i.e., with a more volatile guest, can be instead obtained by the stretching (in the same low temperature range: 170-175 °C) of CC PPO blend films with polystyrene.

Cardiovascular disease (CVD) comprises a range of major clinical cardiac and circulatory diseases, which produce immense health and economic burdens worldwide. Currently, vascular regenerative surgery represents the most employed therapeutic option to treat ischemic disorders, even though not all the patients are amenable to surgical revascularization. Therefore, more efficient therapeutic approaches are urgently required to promote neovascularization. Therapeutic angiogenesis represents an emerging strategy that aims at reconstructing the damaged vascular network by stimulating local angiogenesis and/or promoting de novo blood vessel formation according to a process known as vasculogenesis. In turn, circulating endothelial colony-forming cells (ECFCs) represent truly endothelial precursors, which display high clonogenic potential and have the documented ability to originate de novo blood vessels in vivo. Therefore, ECFCs are regarded as the most promising cellular candidate to promote therapeutic angiogenesis in patients suffering from CVD. The current briefly summarizes the available information about the origin and characterization of ECFCs and then widely illustrates the preclinical studies that assessed their regenerative efficacy in a variety of ischemic disorders, including acute myocardial infarction, peripheral artery disease, ischemic brain disease, and retinopathy. Then, we describe the most common pharmacological, genetic, and epigenetic strategies employed to enhance the vasoreparative potential of autologous ECFCs by manipulating crucial pro-angiogenic signaling pathways, e.g., extracellular-signal regulated kinase/Akt, phosphoinositide 3-kinase, and Ca 2+ signaling. We conclude by discussing the possibility of targeting circulating ECFCs to rescue their dysfunctional phenotype and promote neovascularization in the presence of CVD.

Ischemic heart disease is currently a major cause of mortality and morbidity worldwide. Nevertheless, the actual therapeutic scenario does not target myocardial cell regeneration and consequently, the progression toward the late stage of chronic heart failure is common. Endothelial progenitor cells (EPCs) are bone marrow-derived stem cells that contribute to the homeostasis of the endothelial wall in acute and chronic ischemic disease. Calcium modulation and other molecular pathways (NOTCH, VEGFR, and CXCR4) contribute to EPC proliferation and differentiation. The present review provides a summary of EPC biology with a particular focus on the regulatory pathways of EPCs and describes promising applications for cardiovascular cell therapy.

This study aimed to evaluate the protective effect of a topical antioxidant and ultraviolet (UV) shielding action formulation containing riboflavin and D-α-tocopherol polyethylene glycol succinate (TPGS) vitamin E against corneal UV-induced damage in vivo rabbit eyes. In vivo experiments were performed using male albino rabbits, which were divided into four groups. The control group (CG) did not receive any UV irradiation; the first group (IG) was irradiated with a UV-B-UV-A lamp for 30 min; the second (G30) and third (G60) groups received UV irradiation for 30 and 60 min, respectively, and were topically treated with one drop of the antioxidant and shielding formulation every 15 min, starting one hour before irradiation, until the end of UV exposure. The cornea of the IG group showed irregular thickening, detachment of residual fragments of the Descemet membrane, stromal fluid swelling with consequent collagen fiber disorganization and disruption, and inflammation. The cornea of the G30 group showed edema, a mild thickening of the Descemet membrane without fibrillar collagen disruption and focal discoloration, or inflammation. In the G60 group, the cornea showed a more severe thickening, a more abundant fluid accumulation underneath the Descemet membrane with focal detachment, and no signs of severe tissue alterations, as were recorded in the IG group. Our results demonstrate that topical application of eye drops containing riboflavin and TPGS vitamin E counteracts UV corneal injury in exposed rabbits.

Aflatoxins, and particularly aflatoxin B1 (AFB1), are toxic mycotoxins to humans and farm animal species, resulting in acute and chronic toxicities. At present, AFB1 is still considered a global concern with negative impacts on health, the economy, and social life. In farm animals, exposure to AFB1-contaminated feed may cause several untoward effects, liver damage being one of the most devastating ones. In the present study, we assessed in vitro the transcriptional changes caused by AFB1 in a bovine fetal hepatocyte-derived cell line (BFH12). To boost the cellular response to AFB1, cells were pre-treated with the co-planar PCB 3,3',4,4',5-pentachlorobiphenyl (PCB126), a known aryl hydrocarbon receptor agonist. Three experimental groups were considered: cells exposed to the vehicle only, to PCB126, and to PCB126 and AFB1. A total of nine RNA-seq libraries (three replicates/group) were constructed and sequenced. The differential expression analysis showed that PCB126 induced only small transcriptional changes. On the contrary, AFB1 deeply affected the cell transcriptome, the majority of significant genes being associated with cancer, cellular damage and apoptosis, inflammation, bioactivation, and detoxification pathways. Investigating mRNA perturbations induced by AFB1 in cattle BFH12 cells will help us to better understand AFB1 toxicodynamics in this susceptible and economically important food-producing species., Competing Interests: The authors declare no conflicts of interest.

We propose a distributed Kalman filter for a sensor network under model uncertainty. The distributed scheme is characterized by two communication stages in each time step: in the first stage, the local units exchange their observations and then they can compute their local estimate; in the final stage, the local units exchange their local estimate and compute the final estimate using a diffusion scheme. Each local estimate is computed in order to be optimal according to the least favorable model belonging to a prescribed local ambiguity set. The latter is a ball, in the Kullback-Liebler topology, about the corresponding nominal local model. We propose a strategy to compute the radius, called local tolerance, for each local ambiguity set in the sensor network, rather than keep it constant across the network. Finally, some numerical examples show the effectiveness of the proposed scheme.

Validation testing is a necessary step for inertial measurement unit (IMU) motion analysis for research and clinical use. Optical tracking systems utilize marker models which must be precise in measurement and mitigate skin artifacts. Prosthesis wearers present challenges to optical tracking marker model choice. Seven participants were recruited and underwent simultaneous motion capture from two marker sets; Plug in Gait (PiG) and the Strathclyde Cluster Model (SCM). Variability of joint kinematics within and between subjects was evaluated. Variability was higher for PiG than SCM for all parameters. The within-subjects variability as reported by the average standard deviation (SD), was below 5.6° for all rotations of the hip on the prosthesis side for all participants for both methods, with an average of 2.1° for PiG and 2.5° for SCM. Statistically significant differences in joint parameters caused by a change in the protocol were evident in the sagittal plane (p < 0.05) on the amputated side. Trans-tibial gait analysis was best achieved by use of the SCM. The SCM protocol appeared to provide kinematic measurements with a smaller variability than that of the PiG. Validation studies for prosthesis wearer populations must reconsider the marker protocol for gold standard comparisons with IMUs.

It has long been known that endothelial Ca 2+ signals drive angiogenesis by recruiting multiple Ca 2+ -sensitive decoders in response to pro-angiogenic cues, such as vascular endothelial growth factor, basic fibroblast growth factor, stromal derived factor-1α and angiopoietins. Recently, it was shown that intracellular Ca 2+ signaling also drives vasculogenesis by stimulation proliferation, tube formation and neovessel formation in endothelial progenitor cells. Herein, we survey how growth factors, chemokines and angiogenic modulators use endothelial Ca 2+ signaling to regulate angiogenesis and vasculogenesis. The endothelial Ca 2+ response to pro-angiogenic cues may adopt different waveforms, ranging from Ca 2+ transients or biphasic Ca 2+ signals to repetitive Ca 2+ oscillations, and is mainly driven by endogenous Ca 2+ release through inositol-1,4,5-trisphosphate receptors and by store-operated Ca 2+ entry through Orai1 channels. Lysosomal Ca 2+ release through nicotinic acid adenine dinucleotide phosphate-gated two-pore channels is, however, emerging as a crucial pro-angiogenic pathway, which sustains intracellular Ca 2+ mobilization. Understanding how endothelial Ca 2+ signaling regulates angiogenesis and vasculogenesis could shed light on alternative strategies to induce therapeutic angiogenesis or interfere with the aberrant vascularization featuring cancer and intraocular disorders., Competing Interests: The authors declare no conflict of interest.

Influence of different graphite-based nanofillers on crosslinking reaction of resorcinol, as induced by hexa(methoxymethyl)melamine, is studied. Curing reactions leading from low molecular mass compounds to crosslinked insoluble networks are studied by indirect methods based on Differential Scanning Calorimetry. Reported results show a catalytic activity of graphene oxide (eGO) on this reaction, comparable to that one already described in the literature for curing of benzoxazine. For instance, for an eGO content of 2 wt %, the exothermic crosslinking DSC peak (upon heating at 10 °C/min) shifted 6 °C. More relevantly, oxidized carbon black (oCB) is much more effective as catalyst of the considered curing reaction. In fact, for an oCB content of 2 wt %, the crosslinking DSC peak can be shifted more than 30 °C and a nearly complete crosslinking is already achieved by thermal treatment at 120 °C. The possible origin of the higher catalytic activity of oCB with respect to eGO is discussed.

In this study, two different fillers were prepared from carbon-based ashes, produced from the wooden biomass of a pyro-gasification plant, and starting from lignocellulosic waste. The first type was obtained by dry ball-milling (DBA), while the second one was prepared by oxidation in H 2 O 2 of the dry ball-milled ashes (oDBA). The characterization of the fillers included wide-angle x-ray diffraction (WAXD), thermogravimetric, and Fourier-transform infrared spectroscopy (FTIR) analysis. The DBA and oDBA fillers were then tested as possible catalysts for the crosslinking reaction of a diglycidyl ether of bisphenol A (DGEBA) with a diamine. The cure reaction was studied by means of rheometry and differential scanning calorimetry (DSC). The oDBA filler exhibits both a higher catalytic activity on the epoxide-amine reaction than the DB A sample and improved mechanical properties and glass transition temperature. The results obtained indicate, hence, the potential improvement brought by the addition of carbon-based waste ashes, which allow both increasing the flexural properties and the glass transition temperature of the epoxy resin and reducing the curing time, acting as a catalyst for the crosslinking reaction of the epoxy resin.

The therapeutic scenario for elderly patients with advanced NSCLC has been limited to radiotherapy and chemotherapy. Recently, a novel therapeutic approach based on targeting the immune-checkpoints has showed noteworthy results in advanced NSCLC. PD1/PD-L1 pathway is co-opted by tumor cells through the expression of PD-L1 on the tumor cell surface and on cells within the microenvironment, leading to suppression of anti-tumor cytolytic T-cell activity by the tumor. The success of immune-checkpoints inhibitors in clinical trials led to rapid approval by the FDA and EMA. Currently, data regarding efficacy and safety of ICIs in older subjects is limited by the poor number of elderly recruited in clinical trials. Careful assessment and management of comorbidities is essential to achieve better outcomes and limit the immune related adverse events in elderly NSCLC patients.

Nicotinic acid adenine dinucleotide phosphate (NAADP) gates two-pore channels 1 and 2 (TPC1 and TPC2) to elicit endo-lysosomal (EL) Ca 2+ release. NAADP-induced EL Ca 2+ signals may be amplified by the endoplasmic reticulum (ER) through the Ca 2+ -induced Ca 2+ release mechanism (CICR). Herein, we aimed at assessing for the first time the role of EL Ca 2+ signaling in primary cultures of human metastatic colorectal carcinoma (mCRC) by exploiting Ca 2+ imaging and molecular biology techniques. The lysosomotropic agent, Gly-Phe β-naphthylamide (GPN), and nigericin, which dissipates the ΔpH which drives Ca 2+ refilling of acidic organelles, caused massive Ca 2+ release in the presence of a functional inositol-1,4,5-trisphosphate (InsP₃)-sensitive ER Ca 2+ store. Liposomal delivery of NAADP induced a transient Ca 2+ release that was reduced by GPN and NED-19, a selective TPC antagonist. Pharmacological and genetic manipulations revealed that the Ca 2+ response to NAADP was triggered by TPC1, the most expressed TPC isoform in mCRC cells, and required ER-embedded InsP₃ receptors. Finally, NED-19 and genetic silencing of TPC1 reduced fetal calf serum-induced Ca 2+ signals, proliferation, and extracellular signal-regulated kinase and Akt phoshorylation in mCRC cells. These data demonstrate that NAADP-gated TPC1 could be regarded as a novel target for alternative therapies to treat mCRC.

The goal of this research is to improve preparation of charcoal adducts in a manner suitable for cationic drug release, possibly using an eco-friendly procedure. Charcoal, widely commercialized for human ingestion, is oxidized by hydrogen peroxide in mild conditions. Adducts of a cationic drug (lidocaine hydrochloride, a medication used as local anesthetic) with charcoal are prepared after basification of charcoal and characterized mainly by elemental analysis, wide-angle X-ray diffraction, infrared spectroscopy and thermogravimetry. The drug in the prepared adducts is present in amount close to 30% by weight and can be readily released to both neutral and acidic aqueous solutions. Cation release, as studied by UV spectra of aqueous solutions, is faster in acidic solutions and is faster than for adducts with graphite oxide, which can be prepared only in harsh conditions.

Pulmonary hypertension is an umbrella term including many different disorders causing an increase of the mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg. Recent data revealed a strong association between obesity and pulmonary hypertension. Adiponectin is a protein synthetized by the adipose tissue with pleiotropic effects on inflammation and cell proliferation, with a potential protective role on the pulmonary vasculature. Both in vivo and in vitro studies documented that adiponectin is an endogenous modulator of NO production and interferes with AMP-activated protein kinase (AMPK) activation, mammalian target of rapamycin (mTOR), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ) signaling preventing endothelial dysfunction and proliferation. Furthermore, adiponectin ameliorates insulin resistance by mediating the biological effects of peroxisome proliferator-activated receptor-gamma (PPARγ). Therefore, adiponectin modulation emerged as a theoretical target for the treatment of pulmonary hypertension, currently under investigation. Recently, consistent data showed that hypoglycemic agents targeting PPARγ as well as renin⁻angiotensin system inhibitors and mineralocorticoid receptor blockers may influence pulmonary hemodynamics in different models of pulmonary hypertension.

The acidic vesicles of the endolysosomal (EL) system are emerging as an intracellular Ca 2+ store implicated in the regulation of multiple cellular functions. The EL Ca 2+ store releases Ca 2+ through a variety of Ca 2+ -permeable channels, including Transient Receptor Potential (TRP) Mucolipin 1-3 (TRPML1-3) and two-pore channels 1-2 (TPC1-2), whereas EL Ca 2+ refilling is sustained by the proton gradient across the EL membrane and/or by the endoplasmic reticulum (ER). EL Ca 2+ signals may be either spatially restricted to control vesicle trafficking, autophagy and membrane repair or may be amplified into a global Ca 2+ signal through the Ca 2+ -dependent recruitment of ER-embedded channels. Emerging evidence suggested that nicotinic acid adenine dinucleotide phosphate (NAADP)-gated TPCs sustain multiple cancer hallmarks, such as migration, invasiveness and angiogenesis. Herein, we first survey the EL Ca 2+ refilling and release mechanisms and then focus on the oncogenic role of EL Ca 2+ signaling. While the evidence in favor of TRPML1 involvement in neoplastic transformation is yet to be clearly provided, TPCs are emerging as an alternative target for anticancer therapies.

Background: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca 2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca 2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca 2+ -dependent manner throughout peripheral vasculature., Methods: We analyzed the literature in search of the most recent updates on the potential role of endothelial Ca 2+ signaling in NVC., Results: We found that several neurotransmitters (i.e., glutamate and acetylcholine) and neuromodulators (e.g., ATP) can induce dilation of cerebral vessels by inducing an increase in endothelial Ca 2+ concentration. This, in turn, results in nitric oxide or prostaglandin E2 release or activate intermediate and small-conductance Ca 2+ -activated K⁺ channels, which are responsible for endothelial-dependent hyperpolarization (EDH). In addition, brain endothelial cells express multiple transient receptor potential (TRP) channels (i.e., TRPC3, TRPV3, TRPV4, TRPA1), which induce vasodilation by activating EDH., Conclusions: It is possible to conclude that endothelial Ca 2+ signaling is an emerging pathway in the control of NVC., Competing Interests: The authors declare no conflict of interest.

Small amounts of carbon nanofillers, specifically high-surface-area graphite (HSAG) and more effectively carbon black (CB), are able to solve the well-known problem of degradation (molecular weight reduction) during melt processing, for the most relevant biodegradable polymer, namely poly(lactic acid), PLA. This behavior is shown by rheological measurements (melt viscosity during extrusion experiments and time sweep-complex viscosity) combined with gel permeation chromatography (GPC) experiments. PLA's molecular weight, which is heavily reduced during melt extrusion of the neat polymer, can remain essentially unaltered by simple compounding with only 0.1 wt % of CB. At temperatures close to polymer melting by compounding with graphitic fillers, the observed stabilization of PLA melt could be rationalized by scavenging traces of water, which reduces hydrolysis of polyester bonds. Thermogravimetric analyses (TGA) indicate that the same carbon fillers, on the contrary, slightly destabilize PLA toward decomposition reactions, leading to the loss of volatile byproducts, which occur at temperatures higher than 300 °C, i.e., far from melt processing conditions., Competing Interests: The authors declare no conflict of interest.

Chitosan is a stressing molecule that affects the cells walls and plasma membrane of fungi. For chitosan derivatives, the action mode is not clear. In this work, we used the yeast Ustilago maydis to study the effects of these molecules on the plasma membrane, focusing on physiologic and stress responses to chitosan (CH), oligochitosan (OCH), and glycol-chitosan (GCH). Yeasts were cultured with each of these molecules at 1 mg·mL -1 in minimal medium. To compare plasma membrane damage, cells were cultivated in isosmolar medium. Membrane potential (Δψ) as well as oxidative stress were measured. Changes in the total plasma membrane phospholipid and protein profiles were analyzed using standard methods, and fluorescence-stained mitochondria were observed. High osmolarity did not protect against CH inhibition and neither affected membrane potential. The OCH did produce higher oxidative stress. The effects of these molecules were evidenced by modifications in the plasma membrane protein profile. Also, mitochondrial damage was evident for CH and OCH, while GCH resulted in thicker cells with fewer mitochondria and higher glycogen accumulation., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

This article compares the catalytic activities of oxidized carbon black (oCB) and graphene oxide (eGO) samples on the kinetics of a reaction of diglycidyl ether of bisphenol A (DGEBA) with a diamine, leading to crosslinked insoluble networks. The study is mainly conducted by rheometry and Differential Scanning Calorimetry (DSC). Following the same oxidation procedure, CB samples are more efficiently oxidized than graphite samples. For instance, CB and graphite samples with high specific surface areas (151 and 308 m²/g), as oxidized by the Hummers' method, exhibit O/C wt/wt ratios of 0.91 and 0.62, respectively. Due to the higher oxidation levels, these oCB samples exhibit a higher catalytic activity toward the curing of epoxy resins than fully exfoliated graphene oxide.

Objective: To determine the accuracy of two international Body Mass Index (BMI) cut-offs for classifying obesity compared to the percentage of fat mass (%FM) assessed by Dual-Energy X-ray Absorptiometry (DXA) in a Chilean sample of children and adolescents;, Material and Methods: The subjects studied included 280 children and adolescents (125 girls and 155 boys) aged 8 to 17 years. Weight and height were measured. The BMI was calculated. Two international references (IOFT and WHO) were used as cut-off points. The %FM was assessed by DXA. The receiver operating characteristic (ROC) curve was used to assess the performance of BMI in detecting obesity on the basis of %FM;, Results: A high correlation was observed between the %FM measured by the DXA and the Z-scores of IOTF and WHO scores in the Chilean adolescents separated by sex (r = 0.78-0.80). Differences occurred in both references (IOFT and WHO) in relation to the criteria (p < 0.001). Both references demonstrated a good ability to predict sensitivity (between 84% and 93%) and specificity (between 83% and 88%) in both sexes of children and adolescents;, Conclusions: A high correlation was observed between the Z-score of the BMI with the percentage of fat determined by the DXA. Despite this, the classifications using the different BMI cut-off points showed discrepancies. This suggests that the cut-off points selected to predict obesity in this sample should be viewed with caution.

G protein-coupled receptors (GPCRs) are seven transmembrane-spanning proteins belonging to a large family of cell-surface receptors involved in many intracellular signaling cascades. Despite GPCRs lack intrinsic tyrosine kinase activity, tyrosine phosphorylation of a tyrosine kinase receptor (RTK) occurs in response to binding of specific agonists of several such receptors, triggering intracellular mitogenic cascades. This suggests that the notion that GPCRs are associated with the regulation of post-mitotic cell functions is no longer believable. Crosstalk between GPCR and RTK may occur by different molecular mechanism such as the activation of metalloproteases, which can induce the metalloprotease-dependent release of RTK ligands, or in a ligand-independent manner involving membrane associated non-receptor tyrosine kinases, such as c-Src. Reactive oxygen species (ROS) are also implicated as signaling intermediates in RTKs transactivation. Intracellular concentration of ROS increases transiently in cells stimulated with GPCR agonists and their deliberated and regulated generation is mainly catalyzed by enzymes that belong to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family. Oxidation and/or reduction of cysteine sulfhydryl groups of phosphatases tightly controls the activity of RTKs and ROS-mediated inhibition of cellular phosphatases results in an equilibrium shift from the non-phosphorylated to the phosphorylated state of RTKs. Many GPCR agonists activate phospholipase C, which catalyze the hydrolysis of phosphatidylinositol 4,5-bis-phosphate to produce inositol 1,4,5-triphosphate and diacylglicerol. The consequent mobilization of Ca2+ from endoplasmic reticulum leads to the activation of protein kinase C (PKC) isoforms. PKCα mediates feedback inhibition of RTK transactivation during GPCR stimulation. Recent data have expanded the coverage of transactivation to include Serine/Threonine kinase receptors and Toll-like receptors. Herein, we discuss the main mechanisms of GPCR-mediated cell-surface receptors transactivation and the pathways involved in intracellular responses induced by GPCR agonists. These studies may suggest the design of novel strategies for therapeutic interventions.

The steroid 5α-reductase type II enzyme catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT), and its deficiency leads to undervirilization in 46,XY individuals, due to an impairment of this conversion in genital tissues. Molecular analysis in the steroid 5α-reductase type II gene (SRD5A2) was performed in two 46,XY female siblings. SRD5A2 gene sequencing revealed that the patients were homozygous for p.Gln126Arg missense mutation, which results from the CGA > CAA nucleotide substitution. The molecular result confirmed clinical diagnosis of 46,XY disorder of sex development (DSD) for the older sister and directed the investigation to other family members. Studies on SRD5A2 protein structure showed severe changes at NADPH binding region indicating that structural modeling analysis can be useful to evaluate the deleterious role of a mutation as causing 5α-reductase type II enzyme deficiency.

Chemical sensors are generally based on the integration of suitable sensitive layers and transducing mechanisms. Although inorganic porous materials can be effective, there is significant interest in the use of polymeric materials because of their easy fabrication process, lower costs and mechanical flexibility. However, porous polymeric absorbents are generally amorphous and hence present poor molecular selectivity and undesired changes of mechanical properties as a consequence of large analyte uptake. In this contribution the structure, properties and some possible applications of sensing polymeric films based on nanoporous crystalline phases, which exhibit all identical nanopores, will be reviewed. The main advantages of crystalline nanoporous polymeric materials with respect to their amorphous counterparts are, besides a higher selectivity, the ability to maintain their physical state as well as geometry, even after large guest uptake (up to 10-15 wt%), and the possibility to control guest diffusivity by controlling the orientation of the host polymeric crystalline phase. The final section of the review also describes the ability of suitable polymeric films to act as chirality sensors, i.e., to sense and memorize the presence of non-racemic volatile organic compounds.