Supramolecular assembly of a thermoresponsive steroidal surfactant with an oppositely charged thermoresponsive block copolymer.

Supramolecular rearrangements are crucial in determining the response of stimuli sensitive soft matter systems such as those formed by mixtures of oppositely charged amphiphiles. Here mixtures of this kind were prepared by mixing the cationic block copolymer pAMPTMA30-b-pNIPAAM120 and an anionic surfactant obtained by the modification of the bile salt sodium cholate. As pure components, the two compounds presented a thermoresponsive self-assembly at around 30-35 °C; a micelle formation in the case of the copolymer and a transition from fibers to tubes in the case of the bile salt derivative. When both were present in the same solution they associated into mixed aggregates that showed complex thermoresponsive features. At room temperature, the core of the aggregate was comprised of a supramolecular twisted ribbon of the bile salt derivative. The block copolymers were anchored on the surface of this ribbon through electrostatic interactions between their charged blocks and the oppositely charged heads of the bile salt molecules. The whole structure was stabilized by a corona of the uncharged blocks that protruded into the surrounding solvent. By increasing the temperature to 30-34 °C the mixed aggregates transformed into rods with smooth edges that associated into bundles and clusters, which in turn induced clouding of the solution. Circular dichroism allowed us to follow progressive rearrangements of the supramolecular organization within the complex, occurring in the range of temperature of 20-70 °C.

Relation between lipoprotein subfractions and TSH levels in the cardiovascular risk among women with subclinical hypothyroidism.

OBJECTIVE: Subclinical hypothyroidism (SCH) is a common condition associated with increased cardiovascular risk. A standard treatment is yet to be established, as there is no consensus on the TSH cut-off values which should be used as indicators. Thus, the aim of this study was to assess cardiovascular risk in patients with SCH and to differentiate it according to TSH levels. DESIGN: This was an observational study conducted in an academic medical centre. PATIENTS: The study population consisted of 95 middle-aged women recently diagnosed with SCH and 65 euthyroid controls. MEASUREMENTS: We measured anthropometric parameters, lipid cardiovascular risk markers and lipoprotein subclasses of HDL and LDL. RESULTS: Patients with SCH exhibited a significant increase in triglycerides and atherogenic index of plasma and a significant reduction in HDL-cholesterol with respect to the control group after adjusted by age and BMI. A similar lipid profile was observed in both SCH groups. However, patients with TSH levels higher than 10 mIU/l showed a significant reduction in LDL particle size, which was associated with a higher prevalence of atherogenic pattern B. CONCLUSIONS: Our findings indicate that cardiovascular risk is affected in patients with TSH levels over 10 mIU/l, who have a lipid profile characteristic of atherogenic dyslipidemia.

The CUN-BAE, Deurenberg Fat Mass, and visceral adiposity index as confident anthropometric indices for early detection of metabolic syndrome components in adults.

There is no definition for the metabolic syndrome; visceral obesity, elevated lipids and glucose, and hypertension coexist. The aim of the study is to determine which anthropometric indicators best determine it. Cross-sectional study in 418,343 Spanish workers. Metabolic syndrome was determined using the NCEP-ATPIII, IDF and JIS criteria. The anthropometric variables studied were: body mass index, waist circumference, waist-to-height ratio, CUNBAE, Deuremberg formula, body fat index, body surface index, normalized weight adjusted index, body roundness index, body shape index, visceral adiposity index (VAI), dysfunctional adiposity index, conicity index, metabolic score for visceral fat (METS-VF), waist triglyceride index. In men, the anthropometric indices with the largest areas under the ROC curve are VAI with ATPIII criteria and JIS. If we use the IDF criteria: waist circumference and METS-VF, with the same result. In women, the largest areas under the curve were observed with the Deuremberg formula in both ATPIII and JIS while with the IDF criteria it is METS-VF. The most useful anthropometric indices for identifying metabolic syndrome are CUN-BAE and Deuremberg, followed by the VAI. A single definition of metabolic syndrome should be agreed to determine the best anthropometric index with predictive capacity for its diagnosis.

Current Situation and Prognostic Evolution of Combined Heart-lung Transplantation in a European Union Country.

Background: This study aims to evaluate the entire experience in heart-lung transplantation (HLTx) in a country of the European Union with 47 million inhabitants according to the etiologies that motivated the procedure. Methods: A retrospective study on 1,751 consecutive transplants (HLTx: 78) was performed from 1990 to 2020 in two centers. Overall survival, adjusted for clinical profile and etiological subgroups, was compared. 7 subgroups were considered: 1) Cardiomyopathy with pulmonary hypertension (CM + PH). 2) Eisenmenger syndrome. 3) Congenital heart disease (CHD). 4) Idiopathic pulmonary arterial hypertension (IPAH). 5) Cystic fibrosis. 6) Chronic obstructive pulmonary disease (COPD)/Emphysema. 7) Diffuse interstitial lung disease (ILD). Results: Early mortality was 44% and that of the rest of the follow-up was 31%. There were differences between HTLx and HTx in survival, also comparing groups with a similar clinical profile with propensity score (p= 0.04). Median survival was low in CM + PH (18 days), ILD (29 days) and CHD (114 days), intermediate in Eisenmenger syndrome (600 days), and longer in IPAH, COPD/Emphysema and cystic fibrosis. Conclusion: HLTx has a high mortality. The etiological analysis is of the utmost interest to make the most of the organs and improve survival.

Cognitive-motor interference during gait in patients with Multiple Sclerosis: a mixed methods Systematic Review.

BACKGROUND: Cognitive-motor interference (CMI) has been proposed as a valid marker of daily life impairment in Multiple Sclerosis (MS). The heterogeneity and scarce number of studies regarding CMI in MS has hampered the synthesis of the existing evidence. The present systematic review employed a mixed methods approach with the aim of identifying and describing variables under which CMI is particularly useful to assess patients with MS. RESULTS: MS patients showed significant CMI. The motor variables that were most sensitive in detecting significant CMI were velocity (m/s), cadence (steps/min), and double support (% gait cycle), which was also specific for MS. Among the cognitive tasks, Alternate Alphabet and Serial Subtracting 7 s were sensitive, whereas Verbal Fluency were both sensitive and specific to CMI in MS. CONCLUSIONS: CMI should be assessed in MS with a standardised dual task such as the Verbal Fluency task while walking, with measurements of the double support time and the effect on the cognitive task. The clinical usefulness of CMI in the assessment of patients with MS is discussed.

Management of multidrug resistant Gram-negative bacilli infections in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations.

Solid organ transplant (SOT) recipients are especially at risk of developing infections by multidrug resistant (MDR) Gram-negative bacilli (GNB), as they are frequently exposed to antibiotics and the healthcare setting, and are regulary subject to invasive procedures. Nevertheless, no recommendations concerning prevention and treatment are available. A panel of experts revised the available evidence; this document summarizes their recommendations: (1) it is important to characterize the isolate's phenotypic and genotypic resistance profile; (2) overall, donor colonization should not constitute a contraindication to transplantation, although active infected kidney and lung grafts should be avoided; (3) recipient colonization is associated with an increased risk of infection, but is not a contraindication to transplantation; (4) different surgical prophylaxis regimens are not recommended for patients colonized with carbapenem-resistant GNB; (5) timely detection of carriers, contact isolation precautions, hand hygiene compliance and antibiotic control policies are important preventive measures; (6) there is not sufficient data to recommend intestinal decolonization; (7) colonized lung transplant recipients could benefit from prophylactic inhaled antibiotics, specially for Pseudomonas aeruginosa; (8) colonized SOT recipients should receive an empirical treatment which includes active antibiotics, and directed therapy should be adjusted according to susceptibility study results and the severity of the infection.

Crystal structure of chenodeoxycholic acid, ursodeoxycholic acid and their two 3beta,7alpha- and 3beta,7beta-dihydroxy epimers.

The crystal structures of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (7beta isomer of CDCA) and their other two epimers (3beta,7alpha- and 3beta,7beta-isomers) have been resolved. The four isomers were recrystallized from p-xylene. CDCA crystal is hexagonal P6(5) while the crystals of the other three isomers are orthorhombic (P2(1)2(1)2(1) space group). Only the 3beta,7beta isomer forms an inclusion complex with the solvent with a 1:1 stoichiometry. In all cases, the three hydrogen bond sites (the two hydroxy groups, O3-H and O7-H, and the carboxylic acid group of the side chain, O24bO24a-H) simultaneously act as hydrogen bond donors and acceptors. By considering that O24a is always donor and O24b is always acceptor, the hydrogen bond sequences can be understood on the basis of the interaction between the two hydroxy groups. However the comparison between the four compounds is complicated by the existence of two molecules in the asymmetric unit in the UDCA crystal resulting in that the same hydrogen bond site (for instance O3) can be donor towards two different acceptors (either O7 or O24b). As in the case of the four isomers of deoxycholic acid (Steroids 2004, 69, 379), the other three isomers present a donor-->acceptor sequence, which is O7-->O3 when O3-H is beta and O3-->O7 when O3-H is alpha. The spatial orientation of the carboxylic acid of the side chain is referred to two almost perpendicular planes (defined by (1) the carbon atoms C1/C6-C17/C20 and by (2) the methyl groups C18-C19 and the two carbon atoms to which they are linked, C10 and C13, respectively). Only the side chain of CDCA evidences a positive deviation towards the hydrophobic beta side of the molecule.

Lung graft dysfunction in the early postoperative period after lung and heart lung transplantation.

BACKGROUND: We present a retrospective study of 9 years of experience in the management of graft dysfunction in the early postoperative period after lung transplantation (LT) and heart lung transplantation (HLT). MATERIAL AND METHODS: There were 190 LT and HLT (22.63% single LT, 71.05% bilateral sequential LT, and 7.36% HLT) performed from 1993 to 2002. Hemodynamic and respiratory parameters were monitored during the operative technique and critical care for the first 24 hours. We analyzed ischemic time, bypass need, and type of transplant. RESULTS: Lung graft dysfunction occurred in 37.2% of patients, but only in 12.2% was it severe. Nearly all patients were ventilated on a 50% fraction of inspired oxygen during the first 24-48 hours; 61.56% of patients were extubated before the first 5 postoperative day and 38.43% thereafter. The mean ischemia time for the first lung was 220 +/- 28 minutes: for the second lung, it was 378 +/- 31 minutes. The anesthetic time was 500-600 minutes. The variables associated with a significantly increased graft dysfunction were as follows: bilateral LT, and cardiopulmonary bypass requirement. The residence in the intensive care unit (ICU) was longer for patients with graft dysfunction than for those without that problem. Mortality directly related to graft dysfunction was only 4.07%. CONCLUSIONS: A correlation among graft ischemia and early postoperative morbidity and duration of ICU stay did not have a significant impact on mortality.

Kupffer cells and PIMs in acute experimental African swine fever.

An ultrastructural study of Kupffer cells and pulmonary intravascular macrophages (PIMs) of healthy and African Swine Fever (ASF)-infected pigs was carried out. A vascular perfusion method was performed in order to obtain an optimal intravascular morphology and tissue fixation. The infection developed acute ASF lesions in both organs. Both Kupffer cells and PIMs were studied at different stages of infection. The differences observed in both macrophagic cells from uninfected and infected tissues are shown and discussed.

Apoptosis of thymocytes in experimental African Swine Fever virus infection.

This paper report on the lesions occurred in the thymus in experimental acute African swine fever (ASF). Twenty-one pigs were inoculated with the highly virulent ASF virus (ASFV) isolate Spain-70. Animals were slaughtered from 1 to 7 days post infection (dpi). Three animals with similar features were used as controls. Thymus samples were fixed in 10% buffered formalin solution for histological and immunohistochemical study and in 2.5% glutaraldehyde for ultrastructural examination. For immunohistochemical study, the avidin-biotin-peroxidase complex (ABC) technique was used to demonstrate viral protein 73 and porcine myeloid-histiocyte antigen SWC3 using specific monoclonal antibodies. Cell apoptosis was evaluated by the TUNEL assay. Blood samples were taken daily from all pigs and were used for leukocyte counts. The results of this study show a severe thymocyte apoptosis not related to the direct action of ASFV on these cells, but probably to a quantitative increase in macrophages in the thymus and their activation. A decrease in the percentage of blood lymphocytes was observed at the same time No significant vascular changes were observed in the study. With these results we suggest that ASFV infection of the thymus does not seem to play a critical role in the acute disease. Although severe apoptosis was observed, animals died because of the severe lesions found in the other organs.

Successful prediction of the hydrogen bond network of the 3-oxo-12alpha-hydroxy-5beta-cholan-24-oic acid crystal from resolution of the crystal structure of deoxycholic acid and its three 3,12-dihydroxy epimers.

Crystal structures of p-xylene-crystallized deoxycholic acid (3alpha,12alpha-dihydroxy-5beta-cholan-24-oic acid) and its three epimers (3beta,12alpha-; 3alpha,12beta-; and 3beta,12beta-) have been solved. Deoxycholic acid forms a crystalline (P21) complex with the solvent with a 2:1 stoichiometry whereas crystals of the three epimers do not form inclusion compounds. Crystals of the 3beta,12beta-epimer are hexagonal, whereas the 3alpha,12beta-and 3beta,12alpha-epimers crystallize in the P2(1)2(1)2(1) orthorhombic space group. The three hydrogen bond sites (two hydroxy groups, i. e. O3-H, and O12-H, and the carboxylic acid group of the side chain, O24bO24a-H) simultaneously act as hydrogen bond donors and acceptors. The hydrogen bond network in the crystals was analyzed and the following sequences have been observed: two chains (abcabc... or acbacb... ) and two rings (abc or acb), which constitute a complete set of all the possible sequences which can be drawn for an intermolecular hydrogen bond network formed by three hydrogen bond donor/acceptor sites forming crossing hydrogen bonds. The orientation of O3-H (alpha or beta) determines the sequence of the acceptor and the donor groups involved in the pattern: O24a --> O12 --> O3 --> O24b when it is alpha and O24a --> O3 --> O12--> O24B when it is beta. These observations were used to predict the hydrogen bond network of p-xylene-crystallized 3-oxo,12alpha-hydroxy-5beta-cholan-24-oic acid. This compound has two hydrogen bond donor and three potential hydrogen bond acceptor sites. According to the previous sequence set, this compound should crystallize in the monoclinic P21 system, should form a complex with the solvent, O24b should not participate in the hydrogen bond network, and the chain sequence O24a --> O12 --> O3 would be followed. All predictions were confirmed experimentally.

Morphopathology of the adenohypophysis of chickens in shock induced by Escherichia coli.

We studied modifications in the adenohypophysis of chickens subjected to experimental septic shock by repeated intraperitoneal inoculations with Escherichia coli 026 B6. We observed vascular modifications characterized by capillary dilation and endothelial defects, together with marked perivascular edema and collagen fibers in the groups receiving the most inoculations. Similarly, there was a proliferation of mononuclear cells, belonging mainly to the mononuclear phagocyte system, and plasma cells and lymphocytes. The lesions found in chickens receiving only one inoculation may be evidence of a morphopathological relationship between shock induced by E. coli and lesions that develop in the swollen-head syndrome.

Apoptosis of thymocytes related to cytokine expression in experimental classical swine fever.

Atrophy of the thymic cortex and loss of thymocytes were studied in 32 pigs inoculated with the virulent strain "Alfort" of classical swine fever (CSF) virus and killed at intervals from 2 to 15 days after infection. Immunohistochemical, ultrastructural, ELISA and TUNEL methods were used. The results suggested that direct action of CSF virus on thymocytes played no more than a minor role. The massive lymphoid depletion observed in the thymus, may, however, have been associated with the numerical increase in monocytes-macrophages in this organ, and their secretory activation, leading to synthesis and release of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1alpha and C1q complement component as main chemical mediators, and IL-1beta and IL-6 as minor mediators. These cytokines (TNF-alpha and IL-1alpha) may have played a role in the apoptosis of thymocytes, demonstrated by TUNEL and ultrastructural methods. The pathogenetic mechanism outlined may contribute to the lymphoid depletion observed in others organs in CSF and may explain the lymphopenia characteristic of the disease.

Morphological and immunohistochemical changes in splenic macrophages of pigs infected with classical swine fever.

Classical swine fever (CSF) was induced in 20 pigs by inoculation with a virulent strain of CSF virus to determine sequential changes (2, 4, 7, 10 and 14 days post-inoculation) in the number and morphology of splenic macrophages (red pulp and lymphoid marginal zone) and thus to assess the role of these cells in the pathogenesis of the disease. The first splenic cells to be infected with CSF virus were macrophages in the marginal zone followed by other macrophage populations. The initial phase of CSF was associated with an increase in splenic macrophage numbers in the marginal zone and a decrease in the red pulp. Subsequently, the numbers in the red pulp increased. The study suggested that infection, mobilization and apoptosis of splenic macrophages play an important role in the spread of CSF virus in vivo. Moreover, the secretory changes that occurred in macrophages in the initial phase of the infection suggested that macrophages release chemical mediators capable of modulating pathogenesis.

Pulmonary intravascular macrophages in lungs of pigs inoculated with African swine fever virus of differing virulence.

The role of pulmonary intravascular macrophages (PIM) in a viral infection has been studied by structural and ultrastructural methods with two strains of the African swine fever (ASF) virus: the virulent strain E70 and the attenuated strain E75. Pulmonary intravascular macrophages were the cells of the mononuclear phagocyte system of the lung most involved in the replication of strain E70, showing a marked cytopathic effect and necrosis. Concurrently, their size and number increased sharply. This stimulation of PIMs by the virulent strain of the ASF virus, together with the cytopathic effect, might be the cause of the abundant masses of cell debris found in septal capillaries and thus be related to the pulmonary oedema that characterizes the acute forms of the disease. With the attenuated strain of the ASF virus, stimulation of PIMs, as well as viral replication within them, was also intense, but the cytopathic effect was less. Later, in the course of the infection, the number of PIMs decreased sharply and then alveolar macrophages increased, bearing most of the viral replication and signalling the onset of a pneumonic process.

Classical swine fever: morphological and morphometrical study of pulmonary intravascular macrophages.

To gain further insight into the pathogenesis of classical swine fever (CSF), the changes induced by hog cholera (HC) virus in pulmonary intravascular macrophages (PIMs) were examined. Twelve pigs were inoculated by the intramuscular route with a virulent strain of HC virus (Quillota strain) and killed in groups of three at 4, 7, 10 and 14 days post-inoculation. Immunohistochemical and ultrastructural examination revealed HC virus infection in endothelial cells, PIMs, and interstitial and alveolar macrophages. In addition to viral replication, a predominant feature was the secretory activation of PIMs, characterized by expanded rough endoplasmic reticulum and hyperplastic Golgi complexes. The results obtained suggest that macrophage activation and the subsequent release of pro-inflammatory mediators play an important role in the pathogenesis of CSF.

Soft-tissue osteosarcoma with prominent aneurysmatic bone cyst-like features: a case report.

We describe the cytological features of a soft-tissue high-grade spindle and pleomorphic sarcoma. The smears showed hypercellularity composed of pleomorphic round and elongated cells, and a striking population of multinucleated osteoclast-type giant cells. Microscopically the tumor showed multiple patterns such as highly cellular pleomorphic, less cellular, and hyalinized areas with neoplastic cartilage and osteoid, and areas with hemorrhage and multicystic appearance with numerous osteoclastic giant cells, resembling aneurysmal bone cysts. Immunohistochemical studies showed positivity for vimentin, while chondroid tissue was positive for S-100, and osteoclastic giant cells stained positively for CD68. Due to the varied microscopic patterns, the differential diagnosis included many tumors containing osteoclastic giant cells and osteochondroid tissue.

Detection of African swine fever viral antigens in paraffin-embedded tissues by use of immunohistologic methods and polyclonal antibodies.

Tissues obtained from pigs inoculated with African swine fever virus (ASFV), fixed by vascular perfusion using glutaraldehyde, and embedded in paraffin or araldite were used for an immunohistologic electron microscopic study. To detect ASFV antigens, 4 methods were used on paraffin sections with or without pretreatment of the tissues. Use of biotinylated anti-ASFV antiserum combined with avidin-biotin complex and peroxidase proved to be the most suitable method, and antigen was detected in tissues infected with 2 ASF viruses of different virulence. Use of the glutaraldehyde fixation method should ensure optimal morphologic (structural and ultrastructural) data while allowing an immunohistologic study, and add to knowledge of the pathogenesis of ASF.